Different colors of light lead to different adaptation and activation as determined by high-density EEG.

Light adaptation is crucial for coping with the varying levels of ambient light. Using high-density electroencephalography (EEG), we investigated how adaptation to light of different colors affects brain responsiveness. In a within-subject design, sixteen young participants were adapted first to dim white light and then to blue, green, red, or white bright light (one color per session in a randomized order). Immediately after both dim and bright light adaptation, we presented brief light pulses and recorded event-related potentials (ERPs). We analyzed ERP response strengths and brain topographies and determined the underlying sources using electrical source imaging. Between 150 and 261ms after stimulus onset, the global field power (GFP) was higher after dim than bright light adaptation. This effect was most pronounced with red light and localized in the frontal lobe, the fusiform gyrus, the occipital lobe and the cerebellum. After bright light adaptation, within the first 100ms after light onset, stronger responses were found than after dim light adaptation for all colors except for red light. Differences between conditions were localized in the frontal lobe, the cingulate gyrus, and the cerebellum. These results indicate that very short-term EEG brain responses are influenced by prior light adaptation and the spectral quality of the light stimulus. We show that the early EEG responses are differently affected by adaptation to different colors of light which may contribute to known differences in performance and reaction times in cognitive tests.

Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability.

Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.

Evaluation Study of Pit Run Gravel Asphalt Treated Base Mixtures with Various Percentages of Crushed Limestone, R-217, 1968

In November of 1966, an investigation of the rigid Class I asphalt treated base specification, requiring 70 per cent crushed limestone, was initiated. It was felt that it might be possible to modify the need for crushed particles, in the construction of basis on heavy duty roads, at a savings, by using more local materials, without sacrificing strength and/or durability. This is a short study on typical sources of pit run gravel, with various percentages of limestone. It is conducted with an eye open to the possibility that our specifications may be modified. The possibility that further investigation may be desirable is not ignored.

Bond strength of orthodontic brackets using different light and self-curing cements

The purpose of the study was to evaluate the shear bond strength of stainless steel orthodontic brackets directly bonded to extracted human premolar teeth. Fifty teeth were randomly divided into ¿ve groups: (1) System One (chemically cured composite resin), (2) Light Bond (light-cured composite resin), (3) Vivaglass Cem (self-curing glass ionomer cement), (4) Fuji Ortho LC (light-cured glass ionomer cement) used after 37% orthophosphoric acid¿etching of enamel (5) Fuji Ortho LC without orthophosphoric acid¿etching. The brackets were placed on the buccal and lingual surfaces of each tooth, and the specimens were stored in distilled water (24 hours) at 378C and thermocycled. Teeth were mounted on acrylic block frames, and brackets were debonded using an Instron machine. Shear bond strength values at fracture (Nw)were recorded. ANOVA and Student-Newman-Keuls multiple comparison tests were performed (P , .05). Bonding failure site was recorded by stereomicroscope and analyzed by Chi-square test, selected specimens of each group were observed by scanning electron microscope. System One attained the highest bond strength. Light Bond and Fuji Ortho LC, when using an acid-etching technique, obtained bond strengths that were within the range of estimated bond strength values for successful clinical bonding. Fuji Ortho LC and Vivaglass Cem left an almost clean enamel surface after debracketing.

Deleterious Actions Of Vegf On The Blood Retinal Barrier And Photoreceptor Survival In The Light-damage Model

Purpose: The retinal balance between pro- and anti-angiogenic factors is critical for angiogenesis control, but is also involved in cell survival. We previously reported upregulation of VEGF and photoreceptor (PR) cell death in the Light-damage (LD) model. Preliminary results showed that anti-VEGF can rescue PR from cell death. Thus, we investigated the role of VEGF on the retina and we herein described the effect of anti-VEGF antibody delivered by lentiviral gene transfer in this model.Methods: To characterize the action of VEGF during the LD, we exposed Balb/c mice subretinally injected with LV-anti-VEGF, or not, to 5'000 lux for 1h. We next evaluated the retinal function, PR survival and protein expression (VEGF, VEGFR1/2, Src, PEDF, p38MAPK, Akt, Peripherin, SWL-opsin) after LD. We analyzed Blood retinal barrier (BRB) integrity on flat-mounted RPE and cryosections stained with β-catenin, ZO-1, N-cadherin and albumin.Results: Results indicate that the VEGF pathway is modulated after LD. LD leads to extravascular albumin leakage and BRB breakdown: β-catenin, ZO-1 and N-cadherin translocate to the cytoplasm of RPE cells showing loss of cell cohesion. This phenomenon is in adequacy with the VEGF time-course expression. Assessment of the retinal function reveals that PR rescue correlates with the level of LV-anti-VEGF expression. Rhodopsin content was higher in the LV-anti-VEGF group than in controls and measures of the ONL thickness indicate that LV-anti-VEGF preserves by 82% the outer nuclear layer from degeneration. Outer segments (OS) appeared well organized with an appropriate length in the LV-anti-VEGF group compared to controls, and the expression of SWL-opsin is maintained in the OS without being mislocalized as in the LV-GFP group. Finally, LV-anti-VEGF treatment prevents BRB breakdown and maintained RPE cell integrity.Conclusions: This study involves VEGF in LD and highlights the prime importance of the BRB integrity for PR survival. Taken together, these results show that anti-VEGF is neuroprotective in this model and maintains functional PR layer in LD-treated mice.

Dissociation from BiP and Retrotranslocation of Unassembled Immunoglobulin Light Chains Are Tightly Coupled to Proteasome Activity

Unassembled immunoglobulin light chains expressed by the mouse plasmacytoma cell line NS1 (KNS1) are degraded in vivo with a half-life of 50-60 min in a way that closely resembles endoplasmic reticulum (ER)-associated degradation (Knittler et al., 1995). Here we show that the peptide aldehydes MG132 and PS1 and the specific proteasome inhibitor lactacystin effectively increased the half-life of KNS1, arguing for a proteasome-mediated degradation pathway. Subcellular fractionation and protease protection assays have indicated an ER localization of KNS1 upon proteasome inhibition. This was independently confirmed by the analysis of the folding state of KNS1and size fractionation experiments showing that the immunoglobulin light chain remained bound to the ER chaperone BiP when the activity of the proteasome was blocked. Moreover, kinetic studies performed in lactacystin-treated cells revealed a time-dependent increase in the physical stability of the BiP-KNS1complex, suggesting that additional proteins are present in the older complex. Together, our data support a model for ER-associated degradation in which both the release of a soluble nonglycosylated protein from BiP and its retrotranslocation out of the ER are tightly coupled with proteasome activity.

LIGHT/HVEM/LTβR interaction as a target for the modulation of the allogeneic immune response in transplantation.

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTβR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance.

Advanced light microscopy techniques

This article summarizes the basic principles of light microscopy, with examples of applications in biomedicine that illustrate the capabilities of thetechnique.

GDP and life expectancy in Italy and Spain over the long-run (1861-2008): insights from a timeseries approach

The article presents and discusses long-run series of per capita GDP and life expectancy for Italy and Spain (1861-2008). After refining the available estimates in order to make them comparable and with the avail of the most up-to-date researches, the main changes in the international economy and in technological and sociobiological regimes are used as analytical frameworks to re-assess the performances of the two countries; then structural breaks are searched for and Granger causality between the two variables is investigated. The long-run convergence notwithstanding, significant cyclical differences between the two countries can be detected: Spain began to modernize later in GDP, with higher volatility in life expectancy until recent decades; by contrast, Italy showed a more stable pattern of life expectancy, following early breaks in per capita GDP, but also a negative GDP break in the last decades. Our series confirm that, whereas at the early stages of development differences in GDP tend to mirror those in life expectancy, this is no longer true at later stages of development, when, if any, there seems to be a negative correlation between GDP and life expectancy: this finding is in line with the thesis of a non-monotonic relation between life expectancy and GDP and is supported by tests of Granger causality.

Phototropism: at the crossroads of light-signaling pathways.

Phototropism enables plants to orient growth towards the direction of light and thereby maximizes photosynthesis in low-light environments. In angiosperms, blue-light photoreceptors called phototropins are primarily involved in sensing the direction of light. Phytochromes and cryptochromes (sensing red/far-red and blue light, respectively) also modulate asymmetric hypocotyl growth, leading to phototropism. Interactions between different light-signaling pathways regulating phototropism occur in cryptogams and angiosperms. In this review, we focus on the molecular mechanisms underlying the co-action between photosensory systems in the regulation of hypocotyl phototropism in Arabidopsis thaliana. Recent studies have shown that phytochromes and cryptochromes enhance phototropism by controlling the expression of important regulators of phototropin signaling. In addition, phytochromes may also regulate growth towards light via direct interaction with the phototropins.

Light-regulated interactions with SPA proteins underlie cryptochrome-mediated gene expression.

Cryptochromes are a class of photosensory receptors that control important processes in animals and plants primarily by regulating gene expression. How photon absorption by cryptochromes leads to changes in gene expression has remained largely elusive. Three recent studies, including Lian and colleagues (pp. 1023-1028) and Liu and colleagues (pp. 1029-1034) in this issue of Genes & Development, demonstrate that the interaction of light-activated Arabidopsis cryptochromes with a class of regulatory components of E3 ubiquitin ligase complexes leads to environmentally controlled abundance of transcriptional regulators.

The Oncogene ATF3 Is Potentiated by Cyclosporine A and Ultraviolet Light A.

Cutaneous squamous cell carcinoma (SCC) represents the most important cutaneous complication following organ transplantation. It develops mostly on sun-exposed areas. A recent study showed the role of activating transcription factor 3 (ATF3) in SCC development following treatment with calcineurin inhibitors. It has been reported that ATF3, which may act as an oncogene, is under negative calcineurin/nuclear factor of activated T cells (NFAT) control and is upregulated by calcineurin inhibitors. Still, these findings do not fully explain the preferential appearance of SCC on chronically sun-damaged skin. We analyzed the influence of UV radiation on ATF3 expression and its potential role in SCC development. We found that ATF3 is a specifically induced AP1 member in SCC of transplanted patients. Its expression was strongly potentiated by combination of cyclosporine A and UVA treatment. UVA induced ATF3 expression through reactive oxygen species-mediated nuclear factor erythroid 2-related factor 2 (NRF2) activation independently of calcineurin/NFAT inhibition. Activated NRF2 directly binds to ATF3 promoter, thus inducing its expression. These results demonstrate two mechanisms that independently induce and, when combined together, potentiate the expression of ATF3, which may then force SCC development. Taking into account the previously defined role of ATF3 in the SCC development, these findings may provide an explanation and a mechanism for the frequently observed burden on SCCs on sun-exposed areas of the skin in organ transplant recipients treated by calcineurin inhibitors.

Regional income inequality in Italy in the long run (1871–2001). Patterns and determinants

The chapter presents up-to-date estimates of Italy’s regional GDP, with the present borders, in ten-year benchmarks from 1871 to 2001, and proposes a new interpretative hypothesis based on long-lasting socio-institutional differences. The inverted U-shape of income inequality is confirmed: rising divergence until the midtwentieth century, then convergence. However, the latter was limited to the centrenorth: Italy was divided into three parts by the time regional inequality peaked, in 1951, and appears to have been split into two halves by 2001. As a consequence of the falling back of the south, from 1871 to 2001 we record σ-divergence across Italy’s regions, i.e. an increase in dispersion, and sluggish β-convergence. Geographical factors and the market size played a minor role: against them are both the evidence that most of the differences in GDP are due to employment rather than to productivity and the observed GDP patterns of many regions. The gradual converging of regional GDPs towards two equilibria instead follows social and institutional differences − in the political and economic institutions and in the levels of human and social capital – which originated in pre-unification states and did not die (but in part even increased) in postunification Italy.

Evaluation of the Confirmation Light System at Signalized Intersections in Medium to Large Iowa Communities to Reduce Red Light Running Violations”, TR-657, 2015

Red light running continues to be a serious safety concern for many communities in the United States. The Federal Highway Administration reported that in 2011, red light running accounted for 676 fatalities nationwide. Red light running crashes at a signalized intersections are more serious, especially in high speed corridors where speeds are above 35 mph. Many communities have invested in red light countermeasures including low-cost strategies (e.g. signal backplates, targeted enforcement, signal timing adjustments and improvement with signage) to high-cost strategies (e.g. automated enforcement and intersection geometric improvements). This research study investigated intersection confirmation lights as a low-cost strategy to reduce red light running violations. Two intersections in Altoona and Waterloo, Iowa were equipped with confirmation lights which targeted the through and left turning movements. Confirmation lights enable a single police officer to monitor a specific lane of traffic downstream of the intersection. A before-after analysis was conducted in which a change in red light running violations prior to- and 1 and 3 months after installation were evaluated. A test of proportions was used to determine if the change in red light running violation rates were statistically significant at the 90 and 95 percent levels of confidence. The two treatment intersections were then compared to the changes of red light running violation rates at spillover intersections (directly adjacent to the treatment intersections) and control intersections. The results of the analysis indicated a 10 percent reduction of red light running violations in Altoona and a 299 percent increase in Waterloo at the treatment locations. Finally, the research team investigated the time into red for each observed red light running violation. The analysis indicated that many of the violations occurred less than one second into the red phase and that most of the violation occurred during or shortly after the all-red phase.