Acute myelogenous leukemia (AML) is the most common adult leukemia, characterized by the clonal expansion of immature myeloblasts initiating from rare leukemic stem (LS) cells. To understand the functional properties of human LS cells, we developed a primary human AML xenotransplantation model using newborn nonobese diabetic/severe combined immunodeficient/interleukin (NOD/SCID/IL)2r gamma(null) mice carrying a complete null mutation of the cytokine gamma c upon the SCID background. Using this model, we demonstrated that LS cells exclusively recapitulate AML and retain self-renewal capacity in vivo. They home to and engraft within the osteoblast-rich area of the bone marrow, where AML cells are protected from chemotherapy-induced apoptosis. Quiescence of human LS cells may be a mechanism underlying resistance to cell cycle-dependent cytotoxic therapy. Global transcriptional profiling identified LS cell-specific transcripts that are stable through serial transplantation. These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells.

A poly(3-hexylthiophene) containing an interacting amino chain end enhances the performance of P3HT/CdSe solar cells by increasing the dispersion of CdSe nanocrystals and improving the morphology of the nanocomposite without introducing insulating surfactants.

Cellular redox is controlled by the thioredoxin (Trx) and glutathione (GSH) systems that scavenge harmful intracellular reactive oxygen species (ROS). Oxidative stress also evokes many intracellular events including apoptosis. There are two major pathways through which apoptosis is induced; one involves death receptors and is exemplified by Fas-mediated caspase-8 activation, and another is the stress- or mitochondria-mediated caspase-9 activation pathway. Both pathways converge on caspase-3 activation, resulting in nuclear degradation and cellular morphological change. Oxidative stress induces cytochrome c release from mitochondria and activation of caspases, p53, and kinases, including apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Trx inhibits apoptosis signaling not only by scavenging intracellular ROS in cooperation with the GSH system, but also by inhibiting the activity of ASK1 and p38. Mitochondria-specific thioredoxin (Trx-2) and Trx peroxidases (peroxiredoxins) are suggested to regulate cytochrome c release from mitochondria, which is a critical early step in the apoptotis-signaling pathway. dATP/ATP and reducing factors including Trx determine the manifestation of cell death, apoptosis or necrosis, by regulating the activation process and the activity of redox-sensitive caspases. As mitochondria are the most redox-active organelle and indispensable for cells to initiate or inhibit the apoptosis process, the regulation of mitochondrial function is the central focus in the research field of apoptosis and redox.

The bulk synthesis of the [2 + 2] dimer of fullerene C 60 was achieved by the solid-state mechanochemical reaction of C 60 with KCN by the use of a high-speed vibration milling (HSVM) technique. This reaction took place also by the use of potassium salts such as K 2 CO 3 and CH 3 -CO 2 K, metals such as Li, Na, K, Mg, Al, and Zn, and organic bases such as 4-(dimethylamino)-and 4-aminopyridine. Under optimum conditions, the reaction afforded only the dimer C 120 and unchanged C 60 in a ratio of about 3:7 (by weight) regardless of the reagent used. The dimer C 120 was fully characterized by IR, UV-vis, 13 C NMR, and TOF MS spectroscopies, cyclic voltammetry, and differential scanning calorimetry. Comparison of the IR and 13 C NMR spectral data of C 120 with those reported for all-carbon C 60 polymers implied that the [2 + 2] dimer C 120 represents the essential subunit of these polymers. The dimer C 120 underwent facile dissociation into two C 60 molecules by heat, HSVM treatment, exposure to room light, or electrochemical reduction. The dimer C 120 encapsulating 3 He in one of the C 60 cages was synthesized and was used to confirm the scrambling of a C 60 cage between the monomer and the dimer during the HSVM reaction. A possible mechanism for the selective formation of the dimer C 120 is proposed.