IQ motif selectivity in human IQGAP1: binding of myosin essential light chain and S100B.

IQGAPs are cytoskeletal scaffolding proteins which link signalling pathways to the reorganisation of actin and microtubules. Human IQGAP1 has four IQ motifs each of which binds to calmodulin. The same region has been implicated in binding to two calmodulin-like proteins, the myosin essential light chain Mlc1sa and the calcium and zinc ion binding protein S100B. Using synthetic peptides corresponding to the four IQ motifs of human IQGAP1, we showed by native gel electrophoresis that only the first IQ motif interacts with Mlc1sa. This IQ motif, and also the fourth, interacts with the budding yeast myosin essential light chain Mlc1p. The first and second IQ motifs interact with S100B in the presence of calcium ions. This clearly establishes that S100B can interact with its targets through IQ motifs in addition to interacting via previously reported sequences. These results are discussed in terms of the function of IQGAP1 and IQ motif recognition.

Audley's Light:Flute and Computer

Performance by Elizabeth McNutt

A light microscopic and autoradiographic study of non-irradiated and irradiated ocular wounds

Focal gamma irradiation was used to limit the intraocular extension of scar tissue which typically occurs after posterior perforating injury to the eye. Standard posterior perforating injuries were created in the right eye of forty-eight rabbits, half of which had the site of perforation focally irradiated using a Cobalt 60 ophthalmic plaque. Non-irradiated wounds healed with profuse formation of highly cellular and vascularised granulation tissue which invaded the vitreous to form contractile vitreo-retinal membranes. In irradiated eyes vitreo-retinal membrane formation was infrequent; the wounds showing only sparse granulation tissue with little or no extension into the vitreous cavity. Autoradiographic studies carried out in a second group of 40 animals showed that the episclera was the main source of the proliferating fibroblasts, and cell counts confirmed that the inflammatory and repair responses in irradiated wounds were both delayed and attenuated.

Type Ia supernova bolometric light curves and ejected mass estimates from the nearby supernova factory

We present a sample of normal Type Ia supernovae (SNe Ia) from the Nearby Supernova Factory data set with spectrophotometry at sufficiently late phases to estimate the ejected mass using the bolometric light curve.Wemeasure Ni masses from the peak bolometric luminosity, then compare the luminosity in the Co-decay tail to the expected rate of radioactive energy release from ejecta of a given mass. We infer the ejected mass in a Bayesian context using a semi-analytic model of the ejecta, incorporating constraints from contemporary numerical models as priors on the density structure and distribution of Ni throughout the ejecta. We find a strong correlation between ejected mass and light-curve decline rate, and consequently Ni mass, with ejected masses in our data ranging from 0.9 to 1.4 M. Most fast-declining (SALT2 x <-1) normal SNe Ia have significantly sub-Chandrasekhar ejected masses in our fiducial analysis.

Synthetic light curves and spectra for three-dimensional delayed-detonation models of type ia supernovae

In a companion paper, Seitenzahl et al. have presented a set of three-dimensional delayed detonation models for thermonuclear explosions of near-Chandrasekhar-mass white dwarfs (WDs). Here,we present multidimensional radiative transfer simulations that provide synthetic light curves and spectra for those models. The model sequence explores both changes in the strength of the deflagration phase (which is controlled by the ignition configuration in our models) and the WD central density. In agreement with previous studies, we find that the strength of the deflagration significantly affects the explosion and the observables. Variations in the central density also have an influence on both brightness and colour, but overall it is a secondary parameter in our set of models. In many respects, the models yield a good match to the observed properties of normal Type Ia supernovae (SNe Ia): peak brightness, rise/decline time-scales and synthetic spectra are all in reasonable agreement. There are, however, several differences. In particular, the models are systematically too red around maximum light, manifest spectral line velocities that are a little too high and yield I-band light curves that do not match observations. Although some of these discrepancies may simply relate to approximations made in the modelling, some pose real challenges to the models. If viewed as a complete sequence, our models do not reproduce the observed light-curve width- luminosity relation (WLR) of SNe Ia: all our models show rather similar B-band decline rates, irrespective of peak brightness. This suggests that simple variations in the strength of the deflagration phase in Chandrasekhar-mass deflagration-to-detonation models do not readily explain the observed diversity of normal SNe Ia. This may imply that some other parameter within the Chandrasekhar-mass paradigm is key to the WLR, or that a substantial fraction of normal SNe Ia arise from an alternative explosion scenario.

Kinetics of methylene blue (MB) photocatalyzed reduction and dark regeneration in a colorimetric oxygen sensor

Performance data for a dye based, regenerable oxygen sensor (Mills and Lawrie [1], Mills et al. [2]) are analyzed to develop useful kinetic models for sensor photoactivation (dye reduction) and dark, oxygen detection (dye oxidation). The titania loaded, thin film sensor exhibits an apparent first order photoactivation of the dye, which we demonstrate (Section 3.2 and Fig. 4) is due to a kinetic disguise of a zero order photoreaction occurring through a non-uniformly illuminated sensor film. The observed zero order, slow recovery due to dye oxidation by dioxygen (O2 detection) appears best rationalized by a model assuming a near O2-impermeable skin developing on the sensor surface as solvent is evaporatively removed following sensor film casting and curing.

Effect of roasting on the antioxidant activity of coffee brews

Colombian Arabica coffee beans were roasted to give light, medium, and dark samples. Their aqueous extracts were analyzed by gel filtration chromatography, UV-visible spectrophotometry, capillary electrophoresis, and the ABTS(.+) assay. A progressive decrease in antioxidant activity (associated mainly with chlorogenic acids in the green beans) with degree of roasting was observed with the simultaneous generation of high (HMM) and low molecular mass (LMM) compounds possessing antioxidant activity. Maximum antioxidant activity was observed for the medium-roasted coffee; the dark coffee had a lower antioxidant activity despite the increase in color. Analysis of the gel filtration chromatography fractions showed that the LMM fraction made a greater contribution to total antioxidant activity than the HMM components.

Genetic Background and Light-Dependent Progression of Photoreceptor Cell Degeneration in Prominin-1 Knockout Mice

PURPOSE: Mutations in the Prominin-1 (Prom1) gene are known to cause retinitis pigmentosa and Stargardt disease, both of which are associated with progressive photoreceptor cell death. There are no effective therapies for either disorder. The aim of this study was to investigate the mechanism of the retinal degeneration in Prom1-deficient mouse models.

METHODS: We constructed Prom1 knockout mice with two distinct genetic backgrounds of C57BL/6 and C57BL/6xCBA/NSlc, and investigated the photoreceptor degeneration by means of histology and functional tests.. In addition, we examined the effect of light on the Prom1(-/-) retina by rearing the mice in the normal light/dark cycle and completely dark conditions. Finally, we investigated if the retinoic-acid derivative Fenretinide slowed the pace of retinal degeneration in these mouse models.

RESULTS: The Prom1(-/-)-knockout mice with both backgrounds developed photoreceptor degeneration after eye opening, but the CB57/BL6-background mice developed photoreceptor cell degeneration much faster than the C57BL/6xCBA/NSlc mice, demonstrating genetic background dependency.. Interestingly, our histologic and functional examination showed that the photoreceptor cell degeneration of Prom1-knockout mice was light-dependent, and was almost completely inhibited when the mutant mice were kept in the dark. The Prom1-knockout retina showed strong downregulation of expression of the visual cycle components, Rdh12 and Abca4. Furthermore, administration of Fenretinide, which lowers the level of the toxic lipofuscin, slowed the degeneration of photoreceptor cells.

CONCLUSIONS: These findings improve our understanding of the mechanism of cell death in Prominin-1-related disease and provide evidence that fenretinide may be worth studying in human disease.

Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal.

BACKGROUND: Impaired dark adaptation occurs commonly in vitamin A deficiency. OBJECTIVE: We sought to examine the responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in Nepali women. DESIGN: The dark-adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were also tested at 3 mo postpartum. Results were compared with those for 100 nonpregnant US women of similar age. The amount of light required for pupillary constriction was recorded after bleaching and dark adaptation. RESULTS: Pregnant women receiving vitamin A had better dark-adaptation thresholds (-1.24 log cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta-carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction). Dark-adaptation threshold was associated with serum retinol concentration in pregnant women receiving placebo (P: = 0.001) and in those receiving beta-carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving placebo, mean dark-adaptation thresholds were better during the first trimester (-1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2); P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all 3 groups). CONCLUSIONS: During pregnancy, pupillary dark adaptation was strongly associated with serum retinol concentration and improved significantly in response to vitamin A supplementation. This noninvasive testing technique is a valid indicator of population vitamin A status in women of reproductive age.

Dark room provocative test and extent of angle closure: an anterior segment OCT study.

PURPOSE: To clarify the risk parameters measured by anterior segment optical coherence tomography (AS-OCT) for elevated intraocular pressures (IOP) provoked by the darkroom test and to provide recommendations for its clinical usage. METHODS: Subjects aged >40 years and whose peripheral anterior chambers were ≤1/4 corneal thickness were recruited. The anterior segment of the eye was imaged in sitting position and under both light and dark conditions and biometry was performed using anterior segment optical coherence tomography. The analyzed parameters were: (1) central anterior chamber depth (ACD); (2) anterior chamber width; (3) pupil diameter; (4) iris curvature; (5) lens thickness; and (6) number of meridians with closed angles (NCA). Then the darkroom test was performed and a positive provocative test result was defined as a rise in IOP ≥8 mm Hg after the test. Statistical analyses included: (1) the difference in parameters between positive and negative eyes; (2) the association between posttest IOP and the parameters; and (3) the difference in parameters between the 2 eyes in subjects with the asymmetric results. RESULTS: A total of 70 subjects were recruited. ACD (P=0.022), NCA in light (P<0.001), and NCA in dark (P<0.001) were different significantly between eyes with positive and negative results. There was a strong association between NCA in dark (r=0.755, P<0.001) and the posttest IOP. Among subjects with asymmetric results between the 2 eyes, the ACD was shallower and the lens thickness was larger in the positive eye. CONCLUSIONS: The posttest IOP is determined by the extent of functionally closed angles in the dark. The test may be useful in the early diagnosis of primary angle closure. At the same time, angle configuration should be evaluated to remove false positive result.

Using idiothetic cues to swim a path with a fixed trajectory and distance: Necessary involvement of the hippocampus but not the retrosplenial cortex.

Rats rapidly learned to find a submerged platform in a water maze at a constant distance and angle from the start point, which changed on every trial. The rats performed accurately in the light and dark, but prior rotation disrupted the latter condition. The rats were then retested after receiving cytotoxic hippocampal or retrosplenial cortex lesions. Retrosplenial lesions had no apparent effect in either the light or dark. Hippocampal lesions impaired performance in both conditions but spared the ability to locate a platform placed in the center of the pool. A hippocampal deficit emerged when this pool-center task was run in the dark. The spatial effects of hippocampal damage extend beyond allocentric tasks to include aspects of idiothetic guidance.