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Thinkterior : amazing bespoke kids interiors
\"This book showcases indoor and outdoor spaces created by Thinkterior, a design firm devoted to designing, fabricating and installing environments for children.\"--Provided by publisher.
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Explicit information and practice type can affect the L2 acquisition of plural marking
Previous research has indicated that explicit information (EI) about either the first language (L1) or second language (L2) along with task-essential practice can facilitate L2 learning (e.g., Fernández, 2008; McManus, 2022). However, little research has examined L1–L2 contrastive EI with L1/L2 practice. Targeting plural-marking accuracy, the present study sought to fill this gap by exposing 127 Japanese intermediate learners of English to six online treatment sessions across four conditions: (1) non-contrastive EI (pluralization rule explanation) + L2 practice, (2) contrastive EI + L2 practice, (3) as per Condition 2 + additional L1 practice (application of L2 pluralization to L1 through the Japanese suffix –tachi), and (4) using prepositions as a control, non-contrastive EI (prepositional rule explanation) + L2 practice. Accuracy was tested at pre/post/delayed intervals using an acceptability judgement task (reading) and a picture description task (writing). Statistical analyses demonstrated greater gains from the contrastive variables in the immediate post-test, with L1 practice appearing especially beneficial, despite improvements diminishing in the delayed post-test. Supplementary data from retroactive interviews and questionnaire responses indicated favourable orientations towards the intervention. The study advances understanding of how EI and practice type can be used to maximize L2 learning through web-based practices tailored to the nature of the learning problem.
Journal Article
Perampanel Inhibition of AMPA Receptor Currents in Cultured Hippocampal Neurons
Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (τ∼1 s at 3 µM), concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were 1.5×105 M-1 s-1 and 0.58 s-1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block of non-desensitizing kainate-evoked currents (IC50, 0.56 µM) was similar at all kainate concentrations (3-100 µM), demonstrating a noncompetitive blocking action. Parampanel did not alter the trajectory of AMPA evoked currents indicating that it does not influence AMPA receptor desensitization. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics.
Journal Article
Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity
Many postsynaptic proteins undergo palmitoylation, the reversible attachment of the fatty acid palmitate to cysteine residues, which influences trafficking, localization, and protein interaction dynamics. Both palmitoylation by palmitoyl acyl transferases (PAT) and depalmitoylation by palmitoyl-protein thioesterases (PPT) is regulated in an activity-dependent, localized fashion. Recently, palmitoylation has received attention for its pivotal contribution to various forms of synaptic plasticity, the dynamic modulation of synaptic strength in response to neuronal activity. For instance, palmitoylation and depalmitoylation of the central postsynaptic scaffold protein postsynaptic density-95 (PSD-95) is important for synaptic plasticity. Here, we provide a comprehensive review of studies linking palmitoylation of postsynaptic proteins to synaptic plasticity.
Journal Article
mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming
Alterations in the function of K + channels such as the voltage- and Ca 2+ -activated K + channel of large conductance (BK Ca ) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK Ca splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK Ca ). Through a combination of genetic knockdown and knockout along with a cell permeable BK Ca channel blocker, we show that mitoBK Ca modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the ‘Warburg effect’, thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBK Ca and BK Ca transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK Ca could represent a treatment strategy for selected BC patients in future.
Journal Article
BK channels sustain neuronal Ca2+ oscillations to support hippocampal long-term potentiation and memory formation
Mutations of large conductance Ca
2+
- and voltage-activated K
+
channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL). In line with cognitive impairment in vivo, electrical and chemical long-term potentiation (LTP) in cKO brain slices were impaired in vitro. We further used a genetically encoded fluorescent K
+
biosensor and a Ca
2+
-sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K
+
concentration ([K
+
]
i
) while elevating L-Type Ca
2+
channel- and NMDA receptor-dependent Ca
2+
oscillation frequencies. Both, [K
+
]
i
decrease and Ca
2+
oscillation frequency increase were absent after pharmacological BK inhibition or in cells lacking BK. Our data suggest that L-Type- and NMDAR-dependent BK-mediated K
+
outflow significantly contributes to hippocampal LTP, as well as learning and memory.
Journal Article
Slack K+ channels limit kainic acid-induced seizure severity in mice by modulating neuronal excitability and firing
Mutations of the Na
+
-activated K
+
channel Slack (
KCNT1
) are associated with terrible epilepsy syndromes that already begin in infancy. Here we report increased severity of acute kainic acid-induced seizures in adult and juvenile Slack knockout mice (Slack
−/−
) in vivo. Fittingly, we find exacerbation of cell death following kainic acid exposure in organotypic hippocampal slices as well as dissociated hippocampal cultures from Slack
−/−
in vitro. Furthermore, in cultured Slack
−/−
neurons, kainic acid-triggered Ca
2+
influx and K
+
efflux as well as depolarization-induced tetrodotoxin-sensitive inward currents are higher compared to the respective controls. This apparent changes in ion homeostasis could possibly explain altered action potential kinetics of Slack
−/−
neurons: steeper rise slope, decreased threshold, and duration of afterhyperpolarization, which ultimately lead to higher action potential frequencies during kainic acid application or injection of depolarizing currents. Based on our data, we propose Slack as crucial gatekeeper of neuronal excitability to acutely limit seizure severity.
Mice lacking the Na
+
-activated K
+
channel, Slack, exhibit increased severity of acute kainic-acid induced seizures, suggesting a crucial role for this channel in neuronal excitability.
Journal Article
Explicit information and practice type can affect the L2 acquisition of plural marking
Previous research has indicated that explicit information (EI) about either the first language (L1) or second language (L2) along with task-essential practice can facilitate L2 learning (e.g., Fernández, 2008; McManus, 2022). However, little research has examined L1–L2 contrastive EI with L1/L2 practice. Targeting plural-marking accuracy, the present study sought to fill this gap by exposing 127 Japanese intermediate learners of English to six online treatment sessions across four conditions: (1) non-contrastive EI (pluralization rule explanation) + L2 practice, (2) contrastive EI + L2 practice, (3) as per Condition 2 + additional L1 practice (application of L2 pluralization to L1 through the Japanese suffix – tachi ), and (4) using prepositions as a control, non-contrastive EI (prepositional rule explanation) + L2 practice. Accuracy was tested at pre/post/delayed intervals using an acceptability judgement task (reading) and a picture description task (writing). Statistical analyses demonstrated greater gains from the contrastive variables in the immediate post-test, with L1 practice appearing especially beneficial, despite improvements diminishing in the delayed post-test. Supplementary data from retroactive interviews and questionnaire responses indicated favourable orientations towards the intervention. The study advances understanding of how EI and practice type can be used to maximize L2 learning through web-based practices tailored to the nature of the learning problem.
Journal Article
Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity
Activity-dependent BDNF (brain-derived neurotrophic factor) expression is hypothesized to be a cue for the context-specificity of memory formation. So far, activity-dependent BDNF cannot be explicitly monitored independently of basal BDNF levels. We used the BLEV (
DNF-
-
) reporter mouse to specifically detect activity-dependent usage of
exon-IV and -VI promoters through bi-cistronic co-expression of CFP and YFP, respectively. Enriching acoustic stimuli led to improved peripheral and central auditory brainstem responses, increased Schaffer collateral LTP, and enhanced performance in the Morris water maze. Within the brainstem, neuronal activity was increased and accompanied by a trend for higher expression levels of
exon-IV-CFP and exon-VI-YFP transcripts. In the hippocampus BDNF transcripts were clearly increased parallel to changes in parvalbumin expression and were localized to specific neurons and capillaries. Severe acoustic trauma, in contrast, elevated neither
transcript levels, nor auditory responses, parvalbumin or LTP. Together, this suggests that critical sensory input is essential for recruitment of activity-dependent auditory-specific BDNF expression that may shape network adaptation.
Journal Article