Organization of hue selectivity in macaque V2 thin stripes.

V2 has long been recognized to contain functionally distinguishable compartments that are correlated with the stripelike pattern of cytochrome oxidase activity. Early electrophysiological studies suggested that color, direction/disparity, and orientation selectivity were largely segregated in the thin, thick, and interstripes, respectively. Subsequent studies revealed a greater degree of homogeneity in the distribution of response properties across stripes, yet color-selective cells were still found to be most prevalent in the thin stripes. Optical recording studies have demonstrated that thin stripes contain both color-preferring and luminance-preferring modules. These thin stripe color-preferring modules contain spatially organized hue maps, whereas the luminance-preferring modules contain spatially organized luminance-change maps. In this study, the neuronal basis of these hue maps was determined by characterizing the selectivity of neurons for isoluminant hues in multiple penetrations within previously characterized V2 thin stripe hue maps. The results indicate that neurons within the superficial layers of V2 thin stripe hue maps are organized into columns whose aggregated hue selectivity is closely related to the hue selectivity of the optically defined hue maps. These data suggest that thin stripes contain hue maps not simply because of their moderate percentage of hue-selective neurons, but because of the columnar and tangential organization of hue selectivity.

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS -generating agents

A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2·− ), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2·− is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2·− and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2·−, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells. ^