RESUMO
Kif16A, a member of the kinesin-3 family of motor proteins, has been shown to play crucial roles in inducing mitotic arrest, apoptosis, and mitotic cell death. However, its roles during oocyte meiotic maturation have not been fully defined. In this study, we report that Kif16A exhibits unique accumulation on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Targeted depletion of Kif16A using gene-targeting siRNA disrupts the progression of the meiotic cell cycle. Furthermore, Kif16A depletion leads to aberrant spindle assembly and chromosome misalignment in oocytes. Our findings also indicate that Kif16A depletion reduces tubulin acetylation levels and compromises microtubule resistance to depolymerizing drugs, suggesting its crucial role in microtubule stability maintenance. Notably, we find that the depletion of Kif16A results in a notably elevated incidence of defective kinetochore-microtubule attachments and the absence of BubR1 localization at kinetochores, suggesting a critical role for Kif16A in the activation of the spindle assembly checkpoint (SAC) activity. Additionally, we observe that Kif16A is indispensable for proper actin filament distribution, thereby impacting spindle migration. In summary, our findings demonstrate that Kif16A plays a pivotal role in regulating microtubule and actin dynamics crucial for ensuring both spindle assembly and migration during mouse oocyte meiotic maturation.
Assuntos
Cinesinas , Meiose , Microtúbulos , Oócitos , Fuso Acromático , Animais , Cinesinas/metabolismo , Cinesinas/genética , Meiose/fisiologia , Oócitos/metabolismo , Microtúbulos/metabolismo , Camundongos , Fuso Acromático/metabolismo , Feminino , Actinas/metabolismo , Cinetocoros/metabolismoRESUMO
Many non-small cell lung cancer (NSCLC) patients initially benefiting from gefitinib are confronted with acquired resistance. MiR-138 was previously stated as a growth inhibitor of several cancer cell lines including NSCLC cells and its expression level was significantly lower in gefitinib-resistant cells. The role of miR-138 in NSCLC cell lines PC9 and A549 was verified using methyl thiazolyl tetrazolium (MTT) assay and colony formation assay. Quantitative real-time PCR (RT-PCR) was employed to assess the level of miR-138 in gefitinib-sensitive PC9 cells and gefitinib-resistant PC9GR cells. Bioinformatic algorithms (TargetScan) and rVISTA 2.0 were used to predict binding sites on miR-138 and its target genes. MiR-138 inhibited cell proliferation of PC9 and A549 cells. In PC9GR cells, miR-138 expression was inhibited. Gefitinib treatment negatively regulated miR-138 in PC9 cells. Transfection of PC9GR cells with miR-138 mimics significantly reduced cell viability. MiR-138 was directly regulated by Homeobox A4 (HOXA4) via an HOXA4-binding site on the promoter region. TargetScan predicted numerous miR-138 target genes and EGFR was found to be the functional downstream effector of miR-138. We demonstrated that miR-138 is regulated by HOXA4 and exerts its functions via inhibiting EGFR expression in NSCLC cells.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Regiões 5' não Traduzidas , Células A549 , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Receptores ErbB/genética , Gefitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/química , Humanos , Fatores de TranscriçãoRESUMO
Despite the promising applications of copper selenide nanoparticles, an in-depth elucidation of the inherent properties of tetragonal Cu(2)Se (ß-Cu(2)Se) has not been performed because of the lack of a facile synthesis on the nanoscale and an energy-intensive strategy is usually employed. In this work, a facile wet-chemical strategy, employing HCOOH as reducing agent, has been developed to access single-crystalline metastable ß-Cu(2)Se hyperbranched architectures for the first time. The process avoids hazardous chemistry and high temperatures, and thus opens up a facile approach to the large-scale low-cost preparation of metastable ß-Cu(2)Se hyperbranched architectures. A possible growth mechanism to explain the formation of the ß-Cu(2)Se dendritic morphology has been proposed based on time-dependent shape evolution. Further investigations revealed that the metastable ß-Cu(2)Se can convert into the thermodynamically more stable cubic α-Cu(2-x)Se maintaining the dendritic morphology. An increase in electrical conductivity and a tunable optical response were observed under ambient conditions. This behavior can be explained by the oxidation of the surface of the ß-Cu(2)Se hyperbranched structures, ultimately leading to solid-state phase conversion from ß-Cu(2)Se into superionic conductor α-Cu(1.8)Se, which has potential applications in energy-related devices and sensors.
RESUMO
With H2O-polyols (glycerol, ethylene glycol and polyethylene glycol 400) mix-solvent as media in the NaCl-NaOH-NaNO3 electrolytic system, we developed a simple and efficient electrochemical route for the synthesis of Cu2O nanocrystals with different morphology. The SEM results indicated that electrolytic media and current density had a great influence on the shape of Cu2O crystals. The mono-disperse and uniform sphere Cu2O nanoparticles could be readily obtained in H2O-glycerol (or H2O-ethylene glycol) mix-solvent (1:1 volume ratio) and current density 5 mA/cm2. The sphere Cu2O nanoparticles exhibit excellent adsorption ability for organic dyes (methyl orange, fuchsin acid and methyl blue), which is obviously superior to that of the irregular shape Cu2O crystals prepared in H2O-PEG400 (polyethylene glycol 400) mix-solvent. The present work further confirmed that the adsorption ability of Cu2O crystals was related to their size and shape.
RESUMO
The surface nuclear magnetic resonance (SNMR) technique exploits the NMR phenomenon to quantitatively determine the subsurface distribution of water. In the SNMR sounding system, deeper regions are probed by increasing the pulse moment (the product of the current amplitude and pulse duration). However, the amplitude of the current in the transmitter coil inevitably decays due to the energy loss in the storage capacitor. In practical application, the maximum amplitude of the current in one transmission process is recorded and used as the current amplitude. However, this approach results in errors in calculating the pulse moment and the sensitivity kernel function. In this paper, we build a simulation of the transmission process and the current decay phenomenon appears. From the simulation results, the current amplitude at the end of the pulse is 83% of the maximum. We present a dynamic duty cycle control strategy for a constant excitation current. We calculate the 1D sensitivity kernel function based on the two cases of constant and decaying excitation current, respectively. We observe that the maximum difference between them is greater than 200 nV/m. The inversion results based on a 1D aquifer model containing two aquifers show that the decaying excitation current results in aquifers deeper than the model and the water content of the second aquifer is 50% of the model. A comparative experiment between the decaying excitation current system and the constant excitation current system was conducted in a field experiment. Compared with traditional SNMR instruments, our new system can effectively avoid the phenomenon of excitation current decay in field experiments, and the new SNMR sounding system enables accurate inversion of aquifers.
RESUMO
Alzheimer's disease (AD), the main form of dementia in the elderly, is the most common progressive neurodegenerative disease characterized by rapidly progressive cognitive dysfunction and behavior impairment. AD exhibits a considerable heritability and great advances have been made in approaches to searching the genetic etiology of AD. In AD genetic studies, methods have developed from classic linkage-based and candidate-gene-based association studies to genome-wide association studies (GWAS) and next generation sequencing (NGS). The identification of new susceptibility genes has provided deeper insights to understand the mechanisms underlying AD. In addition to searching novel genes associated with AD in large samples, the NGS technologies can also be used to shed light on the 'black matter' discovery even in smaller samples. The shift in AD genetics between traditional studies and individual sequencing will allow biomaterials of each patient as the central unit of genetic studies. This review will cover genetic findings in AD and consequences of AD genetic findings. Firstly, we will discuss the discovery of mutations in APP, PSEN1, PSEN2, APOE, and ADAM10. Then we will summarize and evaluate the information obtained from GWAS of AD. Finally, we will outline the efforts to identify rare variants associated with AD using NGS.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Animais , HumanosRESUMO
We first demonstrate the rational design and fabrication of novel atomically thick Co3O4 nanosheets (ATCNs) with a specific facet exposed by topochemical transformation from layered intermediate precursors to optimize energy storage. The eminently enhanced lithium storage performance can be attributed not only to the synergistic advantages of inorganic graphene analogues but also the increase of Co(2+) atoms and charge redistribution for ATCNs, which were first revealed by means of synchrotron radiation X-ray absorption near-edge spectroscopy. This work opens the window for the preparation of non-layered atomically thick nanosheets, which will significantly enrich the species of inorganic graphene analogues and optimize energy storage by reasonable materials design and fabrication.