RESUMO
HgSe/CdS core/shell CQD are synthesized, and the changes in the optical absorption and luminescence are investigated. While HgSe quantum dots are naturally n-doped after synthesis, both as colloidal solutions and as films, the HgSe/CdS core/shell dots in solution lose the n-doping, as seen from the optical absorption in solution. However, n-doping is regained in films, and the intraband luminescence of the films of HgSe/CdS is greater than that of the cores. The shell also vastly improves the stability of the quantum dots films against sintering at 200 °C. After annealing at that temperature, the HgSe/CdS films retain a narrow intraband emission and sustain a higher laser power leading to brighter emission at 5 µm.
RESUMO
Itraconazole, a clinically used antifungal drug, was found to possess potent antiangiogenic and anticancer activity that is unique among the azole antifungals. Previous mechanistic studies have shown that itraconazole inhibits the mechanistic target of rapamycin (mTOR) signaling pathway, which is known to be a critical regulator of endothelial cell function and angiogenesis. However, the molecular target of itraconazole that mediates this activity has remained unknown. Here we identify the major target of itraconazole in endothelial cells as the mitochondrial protein voltage-dependent anion channel 1 (VDAC1), which regulates mitochondrial metabolism by controlling the passage of ions and small metabolites through the outer mitochondrial membrane. VDAC1 knockdown profoundly inhibits mTOR activity and cell proliferation in human umbilical vein cells (HUVEC), uncovering a previously unknown connection between VDAC1 and mTOR. Inhibition of VDAC1 by itraconazole disrupts mitochondrial metabolism, leading to an increase in the cellular AMP:ATP ratio and activation of the AMP-activated protein kinase (AMPK), an upstream regulator of mTOR. VDAC1-knockout cells are resistant to AMPK activation and mTOR inhibition by itraconazole, demonstrating that VDAC1 is the mediator of this activity. In addition, another known VDAC-targeting compound, erastin, also activates AMPK and inhibits mTOR and proliferation in HUVEC. VDAC1 thus represents a novel upstream regulator of mTOR signaling in endothelial cells and a promising target for the development of angiogenesis inhibitors.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Itraconazol/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Canal de Ânion 1 Dependente de Voltagem/antagonistas & inibidores , Animais , Antifúngicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Transferência Ressonante de Energia de Fluorescência , Células HEK293 , Células HeLa , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Microscopia de Fluorescência , Dilatação Mitocondrial/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Interferência de RNA , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 1 Dependente de Voltagem/metabolismoRESUMO
Photoconductivity is demonstrated with monodispersed HgSe colloidal quantum dots that are illuminated with radiation resonant with 1S(e)-1P(e) intraband electronic absorption, between 3 and 5 µm. A doping of two electrons per dot gives the lowest dark current, and a detectivity of 8.5 × 10(8) Jones is obtained at 80 K. Photoluminescence of the intraband transition is also observed. The detector properties are discussed in terms of the measured photoluminescence quantum yield, the electron mobility in the 1P(e) state, and the responsivity. The intraband photoresponse allows to fully harness the quantum confined states in colloidal nanostructures, extending the prior limited use of interband transition.
RESUMO
We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone mark was initially identified by MS and then validated by chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. Using chromatin immunoprecipitation sequencing, gene expression analysis and immunodetection, we show that in male germ cells, H4K8hib is associated with active gene transcription in meiotic and post-meiotic cells. In addition, H4K8ac-associated genes are included in and constitute only a subfraction of H4K8hib-labeled genes. The histone Khib mark is conserved and widely distributed, has high stoichiometry and induces a large structural change. These findings suggest its critical role on the regulation of chromatin functions.
Assuntos
Histonas/metabolismo , Hidroxibutiratos/metabolismo , Lisina/metabolismo , Sequência de Aminoácidos , Animais , Epigênese Genética , Genoma , Células HeLa , Humanos , Hidroxibutiratos/química , Masculino , Espectrometria de Massas , Camundongos , Dados de Sequência Molecular , Espermatozoides/metabolismoRESUMO
HgS nanocrystals show a strong mid-infrared absorption and a bleach of the near-infrared band edge, both tunable in energy and reversibly controlled by exposure to solution ions under ambient conditions. The same effects are obtained by applying a reducing electrochemical potential, confirming that the mid-infrared absorption is the intraband transition of the quantum dot. This is the first time that stable carriers are present in the quantum state of strongly confined quantum dot in ambient conditions. The mechanism by which doping is achieved is attributed to the rigid shifts of the valence and conduction band with respect to the environment, similar to the sensitivity of the work function of surfaces to adsorbates.