NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1α and p27

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased p2

Lysine-Rich Extracellular Rings Formed by hβ2 Subunits Confer the Outward Rectification of BK Channels

The auxiliary β subunits of large-conductance Ca2+-activated K+ (BK) channels greatly contribute to the diversity of BK (mSlo1 α) channels, which is fundamental to the adequate function in many tissues. Here we describe a functional element of the extracellular segment of hβ2 auxiliary subunits that acts as the positively charged rings to modify the BK channel conductance. Four consecutive lysines of the hβ2 extracellular loop, which reside sufficiently close to the extracellular entryway of the pore, constitute three positively charged rings. These rings can decrease the extracellular K+ concentration and prevent the Charybdotoxin (ChTX) from approaching the extracellular entrance of channels through electrostatic mechanism, leading to the reduction of K+ inflow or the outward rectification of BK channels. Our results demonstrate that the lysine rings formed by the hβ2 auxiliary subunits influences the inward current of BK channels, providing a mechanism by which current can be rapidly diminished during cellular repolarization. Furthermore, this study will be helpful to understand the functional diversity of BK channels contributed by different auxiliary β subunits

A Class of Fuzzy Variational Inequality Based on Monotonicity of Fuzzy Mappings

Invex monotonicity and pseudoinvex monotonicity of fuzzy mappings are introduced in this paper, and relations are discussed between invex monotonicity (pseudoinvex monotonicity) and invexity (pseudoinvexity) of fuzzy mappings. The existence of a solution to the fuzzy variational-like inequality is discussed, and the existence theorem can be achieved. Furthermore, some extended properties of the fuzzy variational-like inequality are researched. Finally, method of solution is discussed based on genetic algorithm

A Class of Fuzzy Variational Inequality Based on Monotonicity of Fuzzy Mappings

Invex monotonicity and pseudoinvex monotonicity of fuzzy mappings are introduced in this paper, and relations are discussed between invex monotonicity (pseudoinvex monotonicity) and invexity (pseudoinvexity) of fuzzy mappings. The existence of a solution to the fuzzy variational-like inequality is discussed, and the existence theorem can be achieved. Furthermore, some extended properties of the fuzzy variational-like inequality are researched. Finally, method of solution is discussed based on genetic algorithm