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1.
J Biol Chem ; 300(6): 107288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636662

RESUMO

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.


Assuntos
Microscopia Crioeletrônica , AMP Cíclico , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Humanos , Sítios de Ligação , AMP Cíclico/metabolismo , Células HEK293 , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Conformação Proteica
2.
RSC Adv ; 11(5): 2616-2623, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35424246

RESUMO

(Ba0.85Ca0.15)(Zr0.1Ti0.9-x Ce x )O3+ySb (abbreviated as BCZTC x S y ) ceramics were prepared by the conventional solid-state reaction. The effect of the co-doping of Ce and Sb on the phase structure, microstructure, dielectric, and ferroelectric and piezoelectric performances of BCZTC x S y ceramics were investigated systematically. The results indicated that the obtained ceramics are composed of coexisting rhombohedral and tetragonal phases. Significant improvements were also observed in the growth of grain, relative density, as well as electrical performance. After co-doping 0.05 mol% Ce and 0.10 mol% Sb, the sizes of crystalline grains reached the maximum. The following optimal properties were obtained: ε r = 2353, tan δ = 0.026, T c = 109.4 °C, P max = 17.65 µC cm-2, P r = 10.43 µC cm-2, E c = 2.88 kV cm-1, S max = 0.125%, = 417 pm V-1, d 33 = 372 pC N-1. With the increase in dopants, the diffuseness γ increased from 1.663 to 1.733, indicating a more relaxed ferroelectric characteristic. All improvements show that BCZT ceramics co-doped with Ce and Sb could be promising candidates in lead-free devices.

3.
RSC Adv ; 10(44): 26256-26261, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35519746

RESUMO

KTa1-x Nb x O3 with different Ta/Nb ratios (x = 0.15, 0.25, 0.5, 0.75, 0.85) were engineered and prepared by a facile hydrothermal synthesis method to acquire KTN nanoparticles with varied polarity. To investigate the effect of KTN filler with varied polarity on the dielectric performance of polymer matrix composites, KTN/PVDF films were fabricated. The experiment demonstrated the polarity of KTN affected the dielectric performance of the composites. KTa0.5Nb0.5O3 possesses larger polarity with permittivity of 3780 at 1 kHz due to its Curie temperature is closer to room temperature, which contributes 30 wt% doped KTa0.5Nb0.5O3/PVDF composite achieving higher permittivity of 19.5 at 1 kHz than those of the others. Additionally, KTa0.75Nb0.25O3/PVDF composite presents higher breakdown strength than those of the others with an E b value of 164 kV mm-1 when 20 wt% filler is doped. The significant improved dielectric performance by Ta/Nb ratio engineering has the potential of providing new insight on enhancing the energy storage in ceramic-polymer nanocomposites.

4.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(5): 3727-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26329763

RESUMO

In this study, we determined the complete chloroplast genomes from two crucifer species of the Eutrema genus. The sizes of the two cp genomes were 153 948 bp (E. yunnanense) and 153 876 bp (E. heterophyllum). Both genomes have the typical quadripartite structure consisting of a large single copy region, a small single copy region and two inverted repeats. Gene contents and their relative positions of the 132 individual genes (87 protein-coding genes, eight rRNA, and 37 tRNA genes) of either genome were identical to each other. Phylogenetic analysis supports the idea that the currently recognized Eutrema genus is monophyletic and that E. salsugineum and Schrenkiella parvula evolved salt tolerance independently.


Assuntos
Brassicaceae/genética , Genoma de Cloroplastos , Brassicaceae/classificação , Sequências Repetidas Invertidas , Filogenia , Proteínas de Plantas/genética , RNA Ribossômico/genética , RNA de Transferência/genética , Tolerância ao Sal/genética
5.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(6): 4536-4537, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26540005

RESUMO

The complete chloroplast sequence of Ostrya rehderiana is 159 347 bp in length, containing 85 protein-coding genes, 8 ribosomal RNA genes, and 31 transfer RNA genes. The circular genome exhibits a typical chloroplast genome structure comprising a large single copy region of 88 552 bp, a small single copy region of 18 941 bp and a pair of inverted repeats of 25 927 bp. The overall GC content of the chloroplast genome is 36.5%. Phylogenetic analysis of O. rehderiana sequence together with 12 complete chloroplast genomes revealed a basal placement of O. rehderiana within the Fagales species.


Assuntos
Betulaceae/genética , Cloroplastos/genética , Genoma de Cloroplastos , Betulaceae/classificação , DNA de Cloroplastos/química , DNA de Cloroplastos/isolamento & purificação , DNA de Cloroplastos/metabolismo , Fases de Leitura Aberta/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Ribossômico/química , RNA Ribossômico/genética , RNA de Transferência/química , RNA de Transferência/genética
6.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(5): 3527-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26260181

RESUMO

Schrenkiella parvula is an Arabidopsis-related model species used here for studying plant stress tolerance. In this study, the complete chloroplast genome sequence of S. parvula has been reported for the first time. The total length of the chloroplast genome was 153 979 bp, which had a typical quadripartite structure. The annotated plastid genome includes 87 protein-coding genes, 39 tRNA genes and 8 ribosomal RNA genes. The evolutionary relationships revealed by our phylogenetic analysis indicated that S. parvula is closer to the Brassiceae species when compared with Eutrema salsugineum.


Assuntos
Brassicaceae/genética , Cloroplastos/genética , Genoma de Cloroplastos , Genes de RNAr , Tamanho do Genoma , Filogenia , RNA de Transferência/genética , Análise de Sequência de DNA
7.
Ecol Evol ; 5(7): 1513-24, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25897390

RESUMO

It has been hypothesized that species occurring in the eastern and the western Qinghai-Tibet Plateau (QTP) responded differently to climate changes during the Pleistocene. Here, we test this hypothesis by phylogeographic analysis of two sister species, Allium cyathophorum and A. spicata. We sequenced two chloroplast DNA (cpDNA) fragments (accD-psaI and the rpl16 intron) of 150 individuals, and the nuclear (ITS) region of 114 individuals, from 19 populations throughout the distributional ranges of these species. The divergence between the two species was dated at 779 - 714 thousand years before the present and was likely initiated by the most major glaciation in the QTP. Analysis of chlorotype diversity showed that A. spicata, the species occurring in the western QTP, contains much lower genetic diversity (0.25) than A. cyathophorum (0.93), which is distributed in the eastern QTP. Moreover, multiple independent tests suggested that the A. spicata population had expanded recently, while no such expansion was detected in A. cyathophorum, indicating a contrasting pattern of responses to Pleistocene climate changes. These findings highlight the importance of geographical topography in determining how species responded to the climate changes that took place in the QTP during the Pleistocene.

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