The oncogenic RAS-selective lethal small molecule Erastin triggers a unique iron-dependent form of nonapoptotic cell death termed ferroptosis. Ferroptosis is dependent upon the production of intracellular iron-dependent reactive oxygen species (ROS), but not other metals. However, key regulators remain unknown. The heme oxygenase (HO) is a major intracellular source of iron. In this study, the role of heme oxygenase in Erastin-triggered ferroptotic cancer cell death has been investigated. Zinc protoporphyrin IX (ZnPP), a HO-1 inhibitor, prevented Erastin-triggered ferroptotic cancer cell death. Furthermore, Erastin induced the protein and mRNA levels of HO-1 in HT-1080 fibrosarcoma cells. HO-1+/+ and HO-1−/− fibroblast, HO-1 overexpression, and chycloheximide-treated experiments revealed that the expression of HO-1 has a decisive effects in Erastin-triggered cell death. Hemin and CO-releasing molecules (CORM) promote Erastin-induced ferroptotic cell death, not by biliverdin and bilirubin. In addition, hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death.
How does prolonged reduction in retinal-image contrast affect visual-contrast coding? Recent evidence indicates that some forms of long-term visual deprivation result in compensatory perceptual and neural changes in the adult visual pathway. It has not been established whether changes due to contrast adaptation are best characterized as “contrast gain” or “response gain.” We present a theoretical rationale for predicting that adaptation to long-term contrast reduction should result in response gain. To test this hypothesis, normally sighted subjects adapted for four hours by viewing their environment through contrast-reducing goggles. During the adaptation period, the subjects went about their usual daily activities. Subjects' contrast-discrimination thresholds and fMRI BOLD responses in cortical areas V1 and V2 were obtained before and after adaptation. Following adaptation, we observed a significant decrease in contrast-discrimination thresholds, and significant increase in BOLD responses in V1 and V2. The observed interocular transfer of the adaptation effect suggests that the adaptation has a cortical origin. These results reveal a new kind of adaptability of the adult visual cortex, an adjustment in the gain of the contrast-response in the presence of a reduced range of stimulus contrasts, which is consistent with a response-gain mechanism. The adaptation appears to be compensatory, such that the precision of contrast coding is improved for low retinal-image contrasts.
The visual span for reading refers to the range of letters, formatted as in text, that can be recognized reliably without moving the eyes. It is likely that the size of the visual span is determined primarily by characteristics of early visual processing. It has been hypothesized that the size of the visual span imposes a fundamental limit on reading speed [Legge, G. E., Mansfield, J. S., & Chung, S. T. L. (2001). Psychophysics of reading. XX. Linking letter recognition to reading speed in central and peripheral vision. Vision Research, 41, 725-734]. The goal of the present study was to investigate developmental changes in the size of the visual span in school-age children and the potential impact of these changes on children's reading speed. The study design included groups of 10 children in 3rd, 5th, and 7th grade, and 10 adults. Visual span profiles were measured by asking participants to recognize letters in trigrams (random strings of three letters) flashed for 100ms at varying letter positions left and right of the fixation point. Two print sizes (0.25 degrees and 1.0 degrees ) were used. Over a block of trials, a profile was built up showing letter recognition accuracy (% correct) versus letter position. The area under this profile was defined to be the size of the visual span. Reading speed was measured in two ways: with Rapid Serial Visual Presentation (RSVP) and with short blocks of text (termed Flashcard presentation). Consistent with our prediction, we found that the size of the visual span increased linearly with grade level and it was significantly correlated with reading speed for both presentation methods. Regression analysis using the size of the visual span as a predictor indicated that 34-52% of variability in reading speeds can be accounted for by the size of the visual span. These findings are consistent with a significant role of early visual processing in the development of reading skills.
Previous research has shown that perceptual training in peripheral vision, using a letter-recognition task, increases reading speed and letter recognition (Chung, Legge, & Cheung, 2004). We tested the hypothesis that enhanced deployment of spatial attention to peripheral vision explains this training effect. Subjects were pre- and post-tested with 3 tasks at 10° above and below fixation—RSVP reading speed, trigram letter recognition (used to construct visual-span profiles), and deployment of spatial attention (measured as the benefit of a pre-cue for target position in a lexical-decision task). Groups of five normally sighted young adults received 4 days of trigram letter-recognition training in upper or lower visual fields, or central vision. A control group received no training. Our measure of deployment of spatial attention revealed visual-field anisotropies; better deployment of attention in the lower field than the upper, and in the lower-right quadrant compared with the other three quadrants. All subject groups exhibited slight improvement in deployment of spatial attention to peripheral vision in the post-test, but this improvement was not correlated with training-related increases in reading speed and the size of visual-span profiles. Our results indicate that improved deployment of spatial attention to peripheral vision does not account for improved reading speed and letter recognition in peripheral vision.
It is well known that object recognition requires spatial frequencies exceeding some critical cutoff value. People with central scotomas who rely on peripheral vision have substantial difficulty with reading and face recognition. Deficiencies of pattern recognition in peripheral vision, might result in higher cutoff requirements, and may contribute to the functional problems of people with central-field loss. Here we asked about differences in spatial-cutoff requirements in central and peripheral vision for letter and face recognition. The stimuli were the 26 letters of the English alphabet and 26 celebrity faces. Each image was blurred using a low-pass filter in the spatial frequency domain. Critical cutoffs (defined as the minimum low-pass filter cutoff yielding 80% accuracy) were obtained by measuring recognition accuracy as a function of cutoff (in cycles per object). Our data showed that critical cutoffs increased from central to peripheral vision by 20% for letter recognition and by 50% for face recognition. We asked whether these differences could be accounted for by central/peripheral differences in the contrast sensitivity function (CSF). We addressed this question by implementing an ideal-observer model which incorporates empirical CSF measurements and tested the model on letter and face recognition. The success of the model indicates that central/peripheral differences in the cutoff requirements for letter and face recognition can be accounted for by the information content of the stimulus limited by the shape of the human CSF, combined with a source of internal noise and followed by an optimal decision rule.
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