Effect of text‐background lightness combination on visual comfort for reading on a tablet display under different surrounds

Many tablets are designed to change display brightness or color with surround for enhancing visual comfort. Although both color and brightness of a surround may vary a lot, few studies investigated how text‐background lightness combination of a tablet display and surround jointly affect visual comfort, and how display white point affects visual comfort. In this study, 20 observers evaluated visual comfort of 20 text‐background lightness combinations of a 9.7‐inch tablet display through paired comparisons under five surrounds—a dark surround and four ambient lighting conditions comprising two levels of correlated color temperature (CCT)—3500 and 6500 K—and illuminance—300 and 3000 lx. The combination of a black text and a light‐gray background (i.e., L^*_background = 75.33; L^*_text = 1.6) was evaluated the most comfortable when there was ambient light regardless of CCT and illuminance. It was also evaluated the third most comfortable under the dark surround. The observers also evaluated the visual comfort of a dark text on five different white backgrounds under 3500 and 6500 K at 1000 lx. The color of the background that was judged as the most comfortable neither had the whitest appearance nor matched the color of the ambient light. The simultaneous adjustment of the display white point and the text‐background lightness combination merits further investigations.     

Receptive Field Sizes of Nyxnob Mouse Retinal Ganglion Cells

Patients with congenital nystagmus, involuntary eye movements, often have a reduced visual acuity. Some of these patients have a retinal-specific mutation in the protein nyctalopin, which is also present in the Nyx^nob mouse. In these mice, retinal ganglion cells (RGCs) have oscillatory activity, which leads to expanded axonal projections towards the dLGN and consequently to a desegregation of retinal projections to the brain. In this study, we investigate whether the receptive fields of Nyx^nob RGCs have also expanded by measuring the size of their receptive fields using MEA recordings. Contrary to our expectation, relative to wild-type (WT) mice we found receptive field sizes in the Nyx^nob retina had not increased but instead had decreased for green-light preferring RGCs. Additionally, we also found the receptive fields of UV-light preferring RGCs are larger than green-light preferring RGCs in both WT and Nyx^nob mice.     

Preferential labeling of brain cholesterol by {3-14C}D(−)-3-hydroxybutyrate

{3-¹⁴C}D(−)-3-hydroxybutyrate or {2-¹⁴C}glucose was injected subcutaneously into 15-day old suckling rats. The animals were killed 3, 6 and 24 hr later by decapitation. Brain proteins, cholesterol, glycolipids, and phospholipids were extracted and prepared for counting. The {3-¹⁴C}D(−)-3-hydroxybutyrate injected animals showed ca. twofold greater labeling (p<.001) of brain cholesterol compared to {2-¹⁴C}glucose; whereas the {2-¹⁴C}glucose injected animals showed ca. fourfold greater labeling (p<.001) of brain proteins than {3-¹⁴C}D(−)-3-hydroxybutyrate at all time points. The difference in labeling of brain glycolipids and phospholipids was less striking, but greater labeling was apparent at each time point in the {2-¹⁴C}glucose injected animals compared to the {3-¹⁴C}D(−)-3-hydroxybutyrate injected animals. These data suggest that D(−)-3-hydroxybutyrate behaves differently than glucose, being a more direct precursor for brain cholesterol biosynthesis and a less effective precursor for brain protein synthesis. Further studies ascertaining the specific activities of the precursors are necessary to quantitatite the respective contributions of D(−)-3-hydroxybutyrate and glucose to lipid and protein synthesis in the rat brain during development.     

Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction,Photoreceptor Cell Degeneration,and Decreased Visual Function

To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study, we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5^−/− zebrafish had smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post-fertilization, loss of rod and cone opsins were observed in zebrafish exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function and loss of visual photoreceptor pigments. Abnormal levels of RPE65 together with a reduced c-wave amplitude indicate a dysfunctional RPE. The retinal phenotype in Exoc5^−/− mice was present at 20 weeks, but was more pronounced at 27 weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. Together, these data suggest that exocyst-mediated signaling in the RPE is required for RPE structure and function, indirectly leading to photoreceptor degeneration.     

Comparison of visual and automated colorimeter for refined and bleached cottonseed oils

Color as a fundamental quality of edible oils has been determined primarily by visual comparison. The automatic colorimeters introduced recently made it possible to avoid operator variability associated with visual color measurement. The feasibility of using an automatic colorimeter, Colourscan, to measure the color of refined and bleached cottonseed oils was investigated. Good agreement, r²=0.99, between automatic color readings vs. visual color measurement by using the Lovibond-AOCS Color Scale was obtained. Near-linear correlation of light paths from 133.4 to 2.5 mm permits dark oil to be assessed with the automatic colorimeter.     

Overexpression of Neuregulin-1 Type III Has Impact on Visual Function in Mice

Schizophrenia is associated with several brain deficits, including abnormalities in visual processes. Neuregulin-1 (Nrg1) is a family of trophic factors containing an epidermal growth factor (EGF)-like domain. It is thought to play a role in neural development and has been linked to neuropsychiatric disorders. Abnormal Nrg1 expression has been observed in schizophrenia in clinical studies. Moreover, in schizophrenia, there is more and more evidence found about pathological changes of the retina regarding structural, neurochemical and physiological parameters. However, mechanisms of these changes are not well known. To investigate this, we analysed the function of the visual system using electroretinography (ERG) and the measurement of visual evoked potentials (VEP) in transgenic mice overexpressing Nrg1 type III of three different ages (12 weeks, 24 weeks and 55 weeks). ERG amplitudes tended to be higher in transgenic mice than in control mice in 12-week old mice, whereas the amplitudes were almost similar in older mice. VEP amplitudes were larger in transgenic mice at all ages, with significant differences at 12 and 55 weeks (p values between 0.003 and 0.036). Latencies in ERG and VEP measurements did not differ considerably between control mice and transgenic mice at any age. Our data show for the first time that overexpression of Nrg1 type III changed visual function in transgenic mice. Overall, this investigation of visual function in transgenic mice may be helpful to understand corresponding changes that occur in schizophrenia, as they may find use as biomarkers for psychiatric disorders as well as a potential tool for diagnosis in psychiatry.     

Metabolism of [1-14C]docosahexaenoate (22∶6n−3), [1-14C]eicosapentaenoate (20∶5n−3) and [1-14C]linolenate (18∶3n−3) in brain cells from juvenile turbotScophthalmus maximus

The incorporation of [1-¹⁴C]18∶3n−3, (LNA) and [1-¹⁴C]-22∶6n−3 (DHA), and the metabolismvia the desaturase/elongase pathways of [1-¹⁴C]LNA, and [1-¹⁴C]20∶5n−3 (EPA) were studied in brain cells from newly-weaned (1-month-old) and 4-month-old turbot. The rank order of the extent of net incorporation of both LNA and DHA into glycerophospholipids was total diradyl glycerophosphocholines (CPL)> total diradyl glycerophosphoethanolamines (EPL)> phosphatidylserine (PS) and phosphatidylinositol (PI) and was independent of the polyunsaturated fatty acid added, the age of the fish and the time of incubation. However, the rate of incorporation of LNA into total lipid, CPL, EPL and PS was significantly greater than the rate of incorporation of DHA, and there was a significantly greater amount of DHA incorporated into EPL than LNA. There was no significant difference between the amounts of LNA and DHA incorporated into total lipid, CPL, PS and PI. Therefore, little preferential uptake and incorporation of DHA into brain cells was apparent. In 24-h incubations, on average 1.1% and 8.5% of radioactivity from [1-¹⁴C]LNA and [1-¹⁴C]EPA, respectively, were recovered in the DHA fraction. Therefore, LNA cannot contribute significantly to brain DHA levels in the turbot but EPA can. There were no significant differences between the amounts of radioactivity from either [1-¹⁴C]LNA or [1-¹⁴C]EPA recovered in the individual products/intermediates of the desaturase pathways in brain cells from 30-day-old and 120-day-old turbot.     

Knockdown of ephrin-A5 expression by 40% does not affect motor axon growth or migration into the chick hindlimb

Bidirectional signaling between Eph receptor tyrosine kinases and their cell-surface protein signals, the ephrins, comprises one mechanism for guiding motor axons to their proper targets. During projection of motor axons from the lateral motor column (LMC) motor neurons of the spinal cord to the hindlimb muscles in chick embryos, ephrin-A5 has been shown to be expressed in the LMC motor axons until they reach the base of the limb bud and initiate sorting into their presumptive dorsal and ventral nerve trunks, at which point expression is extinguished. We tested the hypothesis that this dynamic pattern of ephrin-A5 expression in LMC motor axons is important for the growth and guidance of the axons to, and into, the hindlimb by knocking down endogenous ephrin-A5 expression in the motor neurons and their axons. No perturbation of LMC motor axon projections was observed in response to this treatment, suggesting that ephrin-A5 is not needed for LMC motor axon growth or guidance.     

Col4a3-/- Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds

Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3^-/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3^-/- mice from three different genetic backgrounds, 129x1/SvJ, C57Bl/6 and Balb/C. male Col4a3^-/- 129x1/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl/6 and Balb/C Col4a3^-/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl/6 Col4a3^-/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.     

Sphingolipid biosynthesis by particulate fractions of normal and “Quaking” mouse brain

No differences were detected in the ability of brain particulate fractions isolated from “Quaking” and normal mice for the incorporation of:¹⁴C-L-serine into 3-keto-dihydrosphingosine; 1-¹⁴C-stearoyl acid and 1-¹⁴C-stearoyl CoA into ceramide and¹⁴C-choline from CDP¹⁴C-choline into sphingomyelin.     

Differential trypsin effect upon (1-14C) acetate incorporation into choline and ethanolamine glycerophosphatides of rat brain and liver

Preincubation of rat brain and liver slices in a medium (5% glucose, 5% fructose, 1% albumin, 1% trypsin, 10 mM phosphate buffer pH 6.0) used to pretreat brain tissue for the separation of cell types was found to uncouple the incorporation of (1-¹⁴C) acetate into ethanolamine phosphoglycerides from that of the choline phosphoglycerides. Incorporation into ethanolamine phosphoglycerides was stimulated in both brain (330%) and liver (780%) slices, while the incorporation of (1-¹⁴C) acetate into choline phosphoglycerides was reduced for both brain (71%) and liver (63%) slices, compared to control values from nonpreincubated material. With (1-¹⁴C) linolenic acid as a precursor, no significant differences were found in incorporation into ethanolamine phosphoglycerides and choline phosphoglycerides.     

Visual comfort as a function of lightness difference between text and background: A cross‐age study using an LCD and a tablet computer

Two experiments were performed to investigate the effects of text‐background lightness difference on visual comfort. A panel of 21 young and 20 older observers in Taiwan participated in Experiment I, using an LCD TV (with a display luminance of 551.8 cd/m²) as the presentation media. The results show that on a light background, visual comfort increases as the lightness difference gets larger and larger. On a dark background, however, the highest visual comfort value can be obtained when there is a moderate lightness difference. There seems to be little effect of age on visual comfort using the LCD TV with regard to the lightness difference. In Experiment II, 20 young and 20 older Taiwanese observers participated, using a tablet computer (with a display luminance of 397.3 cd/m²). According to the results, the larger text‐background lightness difference, the higher visual comfort value for older observers. For young observers, however, the highest visual comfort value can be obtained when there is a moderate, rather than extremely high, lightness difference. These findings can help provide useful guidelines for graphic user interface design in modern e‐reading devices. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 125–134, 2015     

Modulation of p75NTR on Mesenchymal Stem Cells Increases Their Vascular Protection in Retinal Ischemia-Reperfusion Mouse Model

Mesenchymal stem cells (MSCs) are a promising therapy to improve vascular repair, yet their role in ischemic retinopathy is not fully understood. The aim of this study is to investigate the impact of modulating the neurotrophin receptor; p75^NTR on the vascular protection of MSCs in an acute model of retinal ischemia/reperfusion (I/R). Wild type (WT) and p75^NTR-/- mice were subjected to I/R injury by increasing intra-ocular pressure to 120 mmHg for 45 min, followed by perfusion. Murine GFP-labeled MSCs (100,000 cells/eye) were injected intravitreally 2 days post-I/R and vascular homing was assessed 1 week later. Acellular capillaries were counted using trypsin digest 10-days post-I/R. In vitro, MSC-p75^NTR was modulated either genetically using siRNA or pharmacologically using the p75^NTR modulator; LM11A-31, and conditioned media were co-cultured with human retinal endothelial cells (HREs) to examine the angiogenic response. Finally, visual function in mice undergoing retinal I/R and receiving LM11A-31 was assessed by visual-clue water-maze test. I/R significantly increased the number of acellular capillaries (3.2-Fold) in WT retinas, which was partially ameliorated in p75^NTR-/- retinas. GFP-MSCs were successfully incorporated and engrafted into retinal vasculature 1 week post injection and normalized the number of acellular capillaries in p75^NTR-/- retinas, yet ischemic WT retinas maintained a 2-Fold increase. Silencing p75^NTR on GFP-MSCs coincided with a higher number of cells homing to the ischemic WT retinal vasculature and normalized the number of acellular capillaries when compared to ischemic WT retinas receiving scrambled-GFP-MSCs. In vitro, silencing p75^NTR-MSCs enhanced their secretome, as evidenced by significant increases in SDF-1, VEGF and NGF release in MSCs conditioned medium; improved paracrine angiogenic response in HREs, where HREs showed enhanced migration (1.4-Fold) and tube formation (2-Fold) compared to controls. In parallel, modulating MSCs-p75^NTR using LM11A-31 resulted in a similar improvement in MSCs secretome and the enhanced paracrine angiogenic potential of HREs. Further, intervention with LM11A-31 significantly mitigated the decline in visual acuity post retinal I/R injury. In conclusion, p75^NTR modulation can potentiate the therapeutic potential of MSCs to harness vascular repair in ischemic retinopathy diseases.     

Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice

Multidrug resistance-associated protein 1 (MRP1, encoded by the ABCC1 gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[¹¹C]methylpurine. Groups of wild-type, APP/PS1-21 and Abcc1^(−/−) mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity (k_elim) was calculated from time–activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.     

Metabolism of 1,2-(1-14C) dipalmitoyl phosphatidylcholine in the developing brain

Thirteen-day-old rats were divided into two groups; one group received 1,2-(1-¹⁴C) dipalmitoyl phosphatidylcholine and the other 1-¹⁴C palmitic acid in the form of an intraperitoneal injection. One half of the total number of rats in each group was sacrificed 24 hr after injection, and the other half was allowed to survive for 17 days after the injection. Radioactivity incorporated into brain and liver total lipids and into individiual polar lipid components of the brain was determined at both intervals. Phosphatidylcholine was isolated and partially deacylated with phospholipase A₂ fromCrotalus Admanteus venom. The ratio of radioactivity FA 2/FA 1 (fatty acid attached to 2 and 1 carbon of the glycerol moiety) 24 hr after the injection was 8.3, when the tracer was radioactive phosphatidylcholine, compared to only 0.7 when radioactive palmitate was injected. From this different labeling ratio and different pattern of labeling the polar lipid components, it was concluded that the radioactive phosphatidylcholine was not deacylated completely before being taken up directly into the brain. Possibilities are discussed to show that the observed radioactive ratio could result from direct uptake of intact phosphatidylcholine, with little or no restriction from the blood brain barrier system, followed by partial degradation by phospholipase A₁ in the brain itself. Presented in part at the AOCS Meeting, New Orleans, April 1973.     

Enhanced β-oxidative utilization of [1-14C]Palmitate during active myelinogenesis in developing rat brain under nutritional stress

Food restriction was found to impair the incorporation of [1-¹⁴C]palmitate into myelin membrane lipids of developing rat brain. An attempt was made to determine whether this phenomenon is due to differences in the rate of utilization of the labelled precursor or to its enhanced degradationvia β-oxidative pathways. Undernutrition in pups was imposed by food restriction during gestation and lactation. β-Oxidation by brain region homogenates using [1-¹⁴C]palmitate was monitored at days 7, 14 and 21 of postnatal age. There was a significant increase in β-oxidation in the brain regions of undernourished pups, with the cerebrum and cerebellum being more affected than the brain stem. Because developing brain possesses the enzymic potential to utilize ketone bodies, the data may indicate increased usage of palmitate as an energy source in the developing brain of undernourished animals.     

[3-13C] γ-linolenic acid: A new probe for 13C nuclear magnetic resonance studies of arachidonic acid synthesis in the suckling rat

Our objective was to develop a suitable probe to study metabolism of polyunsaturated fatty acids by ¹³C nuclear magnetic resonance (NMR) in the suckling rat pup. [3-¹³C] γ-Linolenic acid was chemically synthesized, and a 20 mg (Experiment 1) or 5 mg (Experiment 2) dose was injected into the stomachs of 6–10-day-old suckling rat pups that were then killed over a 192 h (8 d) time course. ¹³C NMR showed that ¹³C in γ-linolenate peaked in liver total lipids by 12-h post-dosing and that [5-¹³C]-arachidonic acid peaked in both brain and liver total lipids 48–96 h post-dosing. ¹³C enrichment in brain γ-linolenic acid was not detected by NMR, but gas chromatography-combustion-isotope ratio mass spectrometry showed that its mass enrichment in brain phospholipids at 48–96 h post-dosing was 1–2% of that in brain arachidonic acid. ¹³C was present in liver and brain cholesterol and in perchloric acid-extractable water-soluble metabolites in the brain, liver and carcass. We conclude that low but measurable amounts of exogenous γ-linolenic acid do access the suckling rat brain in vivo. The slow time course of [5-¹³C] arachidonic acid appearance in the brain suggests most of it was probably transported there after synthesis elsewhere, probably in the liver. Some carbon from γ-linolenic acid is also incorporated into lipid products other than n−6 long-chain polyunsaturated fatty acids.     

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE^-⁄- and ovariectomized mice (OVX). Female ApoE^-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE^-⁄-/OVX vehicle and ApoE^-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE^-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE^-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE^-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.     

ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke

Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2^wt) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP^wt) and its phosphorylation-deficient mutant RKIP^S153A, known inhibitors of the ERK1/2 signaling cascade. RKIP^wt and RKIP^S153A attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.