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1.
Proc Natl Acad Sci U S A ; 119(33): e2203632119, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35951651

RESUMEN

Epilepsy is a common neurological disorder, which has been linked to mutations or deletions of RNA binding protein, fox-1 homolog (Caenorhabditis elegans) 3 (RBFOX3)/NeuN, a neuronal splicing regulator. However, the mechanism of seizure mediation by RBFOX3 remains unknown. Here, we show that mice with deletion of Rbfox3 in gamma-aminobutyric acid (GABA) ergic neurons exhibit spontaneous seizures and high premature mortality due to increased presynaptic release, postsynaptic potential, neuronal excitability, and synaptic transmission in hippocampal dentate gyrus granule cells (DGGCs). Attenuating early excitatory gamma-aminobutyric acid (GABA) action by administering bumetanide, an inhibitor of early GABA depolarization, rescued premature mortality. Rbfox3 deletion reduced hippocampal expression of vesicle-associated membrane protein 1 (VAMP1), a GABAergic neuron-specific presynaptic protein. Postnatal restoration of VAMP1 rescued premature mortality and neuronal excitability in DGGCs. Furthermore, Rbfox3 deletion in GABAergic neurons showed fewer neuropeptide Y (NPY)-expressing GABAergic neurons. In addition, deletion of Rbfox3 in NPY-expressing GABAergic neurons lowered intrinsic excitability and increased seizure susceptibility. Our results establish RBFOX3 as a critical regulator and possible treatment path for epilepsy.


Asunto(s)
Proteínas de Unión al ADN , Neuronas GABAérgicas , Proteínas del Tejido Nervioso , Neuropéptido Y , Convulsiones , Proteína 1 de Membrana Asociada a Vesículas , Animales , Bumetanida/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Giro Dentado/metabolismo , Antagonistas del GABA/farmacología , Neuronas GABAérgicas/metabolismo , Eliminación de Gen , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuropéptido Y/metabolismo , Convulsiones/genética , Convulsiones/metabolismo , Proteína 1 de Membrana Asociada a Vesículas/genética , Proteína 1 de Membrana Asociada a Vesículas/metabolismo , Ácido gamma-Aminobutírico/metabolismo
2.
Nanoscale ; 15(15): 6954-6959, 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-36988969

RESUMEN

The toxicity of lead presents a critical challenge for the application of perovskite optoelectronics. Lead-free perovskite solar cells were achieved with formamidinium tin iodide (FASnI3) perovskites, exhibiting decent power-conversion efficiencies (PCEs) of up to 14%, with >98% of the initial PCE retained after 3000 h of storage. However, when employed in light-emitting applications, FASnI3-based perovskite LEDs (PeLEDs) show limited stability, with T50 lifetimes of up to 0.25 h at 10 mA cm-2. Here, we improve the stability of FASnI3-based PeLEDs through the inclusion of a two-dimensional precursor phenethylamine iodide (PEAI), allowing controlled crystallization of the mixed-dimensional perovskite emitters. The density of defects is found to be reduced, accompanied by the suppression of oxidation from Sn2+ to Sn4+. Using an optimized perovskite composition, we achieve an EQE of 1.5% (a ∼10-fold improvement over the control devices), a maximum radiance of 145 W sr-1 m-2, and a record-long T50 lifetime of 10.3 h at 100 mA cm-2 for FASnI3-based PeLEDs. Our results illuminate an alternative path toward lead-free PeLED applications.

3.
Commun Biol ; 6(1): 267, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918719

RESUMEN

Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified in the brain, and their functional roles in the brain are not clear. Here we show paternal, but not maternal, expression of MIR125B2 in human but not mouse brain. Moreover, Mir125b-2m-/p- mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2m-/p- mice displayed increased neuronal excitability, increased excitatory synaptic transmission, and decreased inhibitory synaptic transmission. Glutamate ionotropic receptor NMDA type subunit 2A (Grin2a), a key regulator of synaptic plasticity, was physically bound by miR-125b-2 and upregulated in the hippocampus of Mir125b-2m-/p- mice. Taken together, our findings demonstrate MIR125B2 imprinted in human but not mouse brain, mediated learning, memory, and anxiety, regulated excitability and synaptic transmission in hippocampal granule cells, and affected hippocampal expression of Grin2a. Our work provides functional mechanisms of a species-specific imprinted microRNA in the brain.


Asunto(s)
Hipocampo , MicroARNs , Animales , Humanos , Ratones , Hipocampo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Transmisión Sináptica/fisiología
4.
J Phys Chem Lett ; 13(24): 5488-5494, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35687791

RESUMEN

In lead halide perovskites, owing to the strong Fröhlich coupling, carrier dynamics that governs the optoelectronic performance is greatly affected by the lattice vibrations. In this emerging class of materials, injected hot carriers quickly relax by emitting optical phonons, and if this process is sufficiently fast, hot optical phonons can be generated, which may in turn hamper the carrier transport. However, the transient interaction between hot phonons and carriers has not yet been investigated. Herein, we identified the transient absorption feature of hot phonons in lead bromide perovskites and then extracted the hot-phonon dynamics. The hot-phonon decay mechanism was uncovered by temperature-dependent measurements. The hot-phonon decay in lead bromide perovskites was an order of magnitude faster than that in GaAs, attributed to the large anharmonicity arising from the lattice softness and structural fluctuation. The carrier mobility was also transiently suppressed by hot phonons, and the mobility recovery was accompanied by the decay of hot phonons.

5.
J Phys Chem Lett ; 13(2): 704-710, 2022 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-35023748

RESUMEN

Organic additives with amino moieties are effective in improving the properties of archetypical formamidinium (FA)-based hybrid perovskites for photovoltaic and light-emitting applications. However, a detailed understanding of how amino additives affect the perovskite materials is lacking, impeding developments in this area. Here, by investigating the interactions of lead bromide perovskite precursors with phenethylamine (PEA) and its derivatives with small variations in chemical structure, we reveal that only the secondary amine (N-methyl-2-phenylethylamine (N-PEA)) results in strengthened hydrogen bonds with FABr in precursor solutions, allowing the formation of high-quality perovskite films. The photoluminescence quantum efficiencies (PLQEs) of the resultant perovskite samples on widely used charge-transport substrates are retained to 82% of their original values, indicating reduced sensitivity to interfacial nonradiative traps critical to device applications. Using a standard device structure, green perovskite light-emitting diodes with peak external quantum efficiencies of 12.7% at ∼500 cd m-2 and operational lifetimes (T50) exceeding 10 h (at 100 cd m-2) are obtained.

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