The 8;21 translocation is a common chromosomal abnormality in acute myeloid leukemia (AML). We recently identified a naturally occurring leukemogenic splice variant, AML1-ETO9a (acute myeloid leukemia-1 transcription factor and the eighttwenty-one corepressor-9a), of t(8;21). To understand the leukemic potential of AML1-ETO9a, we performed microarray analysis with the murine multipotential hematopoietic FDCPmix A4 cell line. We identified changes in expression of various genes including CD44. CD44 is a type I transmembrane protein and functions as the major cellular adhesion molecule for hyaluronic acid, a component of the extracellular matrix. CD44 is expressed in most human cell types and is implicated in myeloid leukemia pathogenesis. We show that the presence of AML1-ETO9a significantly increased the expression of CD44 at both RNA and protein levels. Furthermore, the CD44 promoter is bound by AML1-ETO9a and AML1-ETO at the chromatin level. In addition, in the AML1-ETO9a leukemia mouse model CD44 is regulated in a cell context-dependent manner. Thus, our observations suggest that AML1-ETO and its splice variant AML1-ETO9a are able to regulate the expression of the CD44 gene, linking the 8;21 translocation to the regulation of a cell adhesion molecule that is involved in the growth and maintenance of the AML blast/stem cells.
Recently, more and more attention has been given to a semiconductor oxide-based surface-enhanced Raman spectroscopy substrate for its great stability and biocompatibility. However, its poor SERS sensitivity limits the applications of semiconductor oxide SERS substrates. In this paper, we provide a facile reduction method to modulate oxygen vacancy concentrations in oxide SERS substrates. Using MoO2 as an example, the resonance coupling as well as charge transfer between the semiconductor oxide SERS substrate and the target molecules were promoted for the reason of artificial oxygen vacancy embodied in the Raman signals being improved. By using the TEM, SEM, and XPS measurements, we confirmed that we successfully prepared defective MoO2–x with a polycrystalline surface. MoO2–x modulated oxygen vacancy treated with 6 wt % Li shows a very high detection sensitivity of 10–8 M (4.79 ug/L) for R6G, and the intensity of the Raman signal was highly enhanced. Because of the existence of defective energy levels, resonance coupling, as well as charge transfer between semiconductor and molecules, was obviously promoted. More importantly, the method of modulating oxygen vacancy can be widely used in semiconductor oxide materials for its chemical enhancement capacity can be promoted by artificial oxygen vacancy.
AML1/RUNX1 is a critical transcription factor in hematopoietic cell differentiation and proliferation. From the AML1 gene, at least three isoforms, AML1a, AML1b and AML1c, are produced through alternative splicing. AML1a interferes with the function of AML1b/1c, which are often called AML1. In this study, we found a higher expression level of AML1a in acute lymphoblastic leukemia and acute myeloid leukemia (AML)-M2 patients in comparison to the controls. Additionally, AML1a represses transcription of promoter of macrophage colony-stimulating factor receptor mediated by AML1b, indicating that AML1a antagonized the effect of AML1b. To investigate the role of AML1a in hematopoiesis and leukemogenesis in vivo, murine bone marrow mononuclear cells were transduced with AML1a and then transplanted into lethally irradiated mice, which developed lymphoblastic leukemia after transplantation. Taken together, these results indicate that overexpression of AML1a may be an important contributing factor to leukemogenesis.
the dimensionless figure of merit zT = PF•T/κ = α 2 σT/(κ e + κ L ), where α, σ, T, κ e , and κ L are the Seebeck coefficient, electrical conductivity, absolute temperature, and electronic and lattice contributions to the total thermal conductivity, respectively. [3] PF denotes the TE power factor that characterizes electrical transport performance. In practice, the average power factor (PF avg ) is directly proportional to the output power density of TE devices. [4] Therefore, for practical application, a higher PF avg is more desirable for achieving a large output power. In principle, PF and PF avg are both determined by electronic band structure and optimal carrier concentration. [5][6][7] Several strategies have been proposed to enhance both PF and PF avg . For example, Pei et al. [8] showed that a high peak PF can be achieved in PbTe by increasing the band degeneracy; Zhu et al. [9] demonstrated that FeNb 1−x Ti x Sb reaches high PF via reducing band effective mass, which results in high carrier mobility. In recent years, it has been elucidated that grain boundaries also play an important role in carrier scattering for certain TE compounds. For instance, Zhao et al. [10,11] revealed that both p and n-type SnSe single crystals that are free of grain boundaries exhibit high PFs; Snyder et al. [12,13] discovered that PF of Mg 3 Sb 2 -based Thermoelectric materials are typically highly degenerate semiconductors, which require high carrier concentration. However, the efficiency of conventional doping by replacing host atoms with alien ones is restricted by solubility limit, and, more unfavorably, such a doping method is likely to cause strong charge-carrier scattering at ambient temperature, leading to deteriorated electrical performance. Here, an unconventional doping strategy is proposed, where a small trace of alien atoms is used to stabilize cation vacancies in Cu 3 SbSe 4 by compositing with CuAlSe 2 , in which the cation vacancies rather than the alien atoms provide a high density of holes. Consequently, the hole concentration enlarges by six times but the carrier mobility is well maintained. As a result, a record-high average power factor of 19 µW cm −1 K −2 in the temperature range of 300-723 K is attained. Finally, with further reduced lattice thermal conductivity, a peak zT value of 1.4 and a record-high average zT value of 0.72 are achieved within the diamond-like compounds. This new doping strategy not only can be applied for boosting the average power factor for thermoelectrics, but more generally can be used to maintain carrier mobility for a variety of semiconductors that need high carrier concentration.
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