Detection of retinal dysfunction induced by HCN channel inhibitors using multistep light stimulus and long-duration light stimulus ERG in rats.

Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor, has been reported to induce photosensitivity-related visual disturbances such as phosphene in humans. Ivabradine-induced visual disturbances are caused by inhibition of HCN channels in the retina, and the mechanisms have been verified using HCN channel knockout mice and electroretinography (ERG). However, in rats, classical ERG using single flash light stimulus with standard analyses of waveform amplitude and latency has not revealed abnormal retinal function after administration of ivabradine. To verify whether retinal dysfunction after ivabradine administration was detectable in rats, we performed ERG using multistep flash light stimulation at the time when plasma concentration of ivabradine was high. Furthermore, the mechanism of the change in the waveform that appeared after the b-wave was investigated. Ivabradine and cilobradine, a selective HCN channel inhibitor, were administered subcutaneously to rats at 4-40 mg/kg as a single dose, and flash or long-duration ERG recordings at each light stimulus luminance were conducted 1.5 h after administration. Plasma and retinal concentrations of both compounds were measured immediately after the ERG recordings. In the flash ERG, prolongation of a- and/or b-wave latencies were detected at each light stimulus, and dose-dependent waveform changes after the b-wave were recorded at the specific light stimulus luminance for both compounds. These ERG changes increased in response to increasing plasma and retinal concentrations for both ivabradine and cilobradine. In the long-duration light stimulus ERG, a change in the waveform of the b-wave trough and attenuation of the c-wave were recorded, suggesting that the feedback control in the photoreceptor cells may be inhibited. This study revealed that the retinal dysfunction by HCN channel inhibitors in rats can be detected by multistep light stimulus ERG. Additionally, we identified that the inhibition of feedback current and the sustained responses in the photoreceptor cells cause the retinal dysfunction of HCN channel inhibitors in rats.

The Synergistic Effects of Environmental and Genetic Factors on the Regulation of Anthocyanin Accumulation in Plant Tissues.

Anthocyanin accumulation is responsible for the coloration of apple fruit, and their accumulation depends on the expression of anthocyanin biosynthesis-related genes. Light is an environmental stimulus that induces fruit color by regulating genes involved in the anthocyanin biosynthesis pathway. In this study, the roles of light and genetic factors on fruit coloration and anthocyanin accumulation in apple fruit were investigated. Three genes in the anthocyanin biosynthesis pathway, MdCHS, MdANS, and MdUFGT1, were synthesized and cloned into a viral-based expression vector system for transient expression in 'Ruby S' apple fruits. Apple fruits were agroinfiltrated with expression vectors harboring MdCHS, MdANS, and MdUFGT1. Agroinfiltrated apple fruits were then either kept in the dark (bagged fruits) or exposed to light (exposed fruits). The agroinfiltrated fruits showed significantly different coloration patterns, transcript expression levels, and anthocyanin accumulation compared to the control fruits. Moreover, these parameters were higher in exposed fruits than in bagged fruits. For stable expression, MdCHS was introduced into a binary vector under the control of the rice α-amylase 3D (RAmy3D) promoter. The ectopic overexpression of MdCHS in transgenic rice calli showed a high accumulation of anthocyanin content. Taken together, our findings suggest that light, together with the overexpression of anthocyanin biosynthesis genes, induced the coloration and accumulation of anthocyanin content in apple fruits by upregulating the expression of the genes involved in the anthocyanin biosynthesis pathway.

The Simultaneous Assessment of Time and Motion Response during Dual Tasks.

Measurement of reaction time in clinical settings is generally employed to assess cognitive abilities by having a subject perform standard simple tests. In this study, a new method of measuring response time (RT) was developed using a system composed of LEDs that emit light stimuli and are equipped with proximity sensors. The RT is measured as the time taken by the subject to turn off the LED target by moving the hand towards the sensor. Through an optoelectronic passive marker system, the associated motion response is assessed. Two tasks of 10 stimuli each were defined: simple reaction time and recognition reaction time tasks. To validate the method implemented to measure RTs, the reproducibility and repeatability of the measurements were estimated, and, to test the method's applicability, a pilot study was conducted on 10 healthy subjects (6 females and 4 males, age = 25 ± 2 years), reporting, as expected, that the response time was affected by the task's difficulty. Unlike commonly used tests, the developed method has proven to be adequate for the simultaneous evaluation of the response in terms of time and motion. Furthermore, thanks to the playful nature of the tests, this method could also be used for clinical and pediatric applications to measure the impact of motor and cognitive impairments on RT.

Among-individual variation in the swimming behaviour of the amphipod Gammarus pulex under dark and light conditions.

In recent years, considerable computational advancements have been made allowing automated analysis of behavioural endpoints using video cameras. However, the results of such analyses are often confounded by a large variation among individuals, making it problematic to derive endpoints that allow distinguishing treatment effects in behavioural studies. In this study, we quantitatively analysed the effects of light conditions on the swimming behaviour of the freshwater amphipod Gammarus pulex by high-throughput tracking, and attempted to unravel among individual variation using size and sex. For this, we developed the R-package Kinematics, allowing for the rapid and reproducible analysis of the swimming behaviour (speed, acceleration, thigmotaxis, curvature and startle response) of G. pulex, as well as any other organism. Our results show a considerable amount of variation among individuals (standard deviation ranging between 5 and 115 % of the average swimming behaviour). The factors size and sex and the interaction between the two only explained a minor part of this found variation. Additionally, our study is the first to quantify the startle response in G. pulex after the light is switched on, and study the variability of this response between individuals. To analyse this startle response, we established two metrics: 1) startle response magnitude (the drop in swimming velocity directly after the light switches on), and 2) startle response duration (the time it takes to recover from the drop in swimming velocity to average swimming speed). Almost 80 % of the individuals showed a clear startle response and, therefore, these metrics demonstrate a great potential for usage in behavioural studies. The findings of this study are important for the development of appropriate experimental set-ups for behavioural experiments with G. pulex.

Investigation of mechanisms underlying a light approaching behavior in a house gecko by comparative and learning experiments.

Nocturnal predators of many taxa are known to come to artificial light at night for foraging on clumped food resources. Both innate and acquired light preferences seem to be possible mechanisms of light approaching behavior although empirical tests are lacking in most nocturnal predators. Here, using a Japanese gecko Gekko japonicus, we investigated whether geckos have a light preference and how foraging experiences under the light reinforce light approaching tendency. In a comparative experiment, there was no difference in light approaching behavior between urban and suburban geckos irrespective of their original light habitats. In an associative learning experiment, geckos did not significantly change light approaching behavior even after repeated opportunities to forage crickets near a lamp in the laboratory setting. These results imply that light approaching behavior of Japanese geckos may not be easily reinforced by foraging experiences under the light. Although we often witness geckos coming to artificial light at night, our findings may not suggest their light preference. Geckos may approach the light-up foraging spot based on other cues relating to the artificial light environment.

Aggregation-Induced Emission Luminogens with Photoresponsive Behaviors for Biomedical Applications.

Fluorescent biomedical materials can visualize subcellular structures and therapy processes in vivo. The aggregation-induced emission (AIE) phenomenon helps suppress the quenching effect in the aggregated state suffered by conventional fluorescent materials, thereby contributing to design strategies for fluorescent biomedical materials. Photoresponsive biomedical materials have attracted attention because of the inherent advantages of light; i.e., remote control, high spatial and temporal resolution, and environmentally friendly characteristics, and their combination with AIE facilitates development of fluorescent molecules with efficient photochemical reactions upon light irradiation. In this review, organic compounds with AIE features for biomedical applications and design strategies for photoresponsive AIE luminogens (AIEgens) are first summarized briefly. Applications are then reviewed, with the employment of photoresponsive and AIE-active molecules for photoactivation imaging, super-resolution imaging, light-induced drug delivery, photodynamic therapy with photochromic behavior, and bacterial targeting and killing being discussed at length. Finally, the future outlook for AIEgens is considered with the aim of stimulating innovative work for further development of this field.

Clinical factors affecting pupillary light reflex parameters: a single-centre, cross-sectional study.

PURPOSE: To evaluate the effects of stimulus intensity, aging, sex, smoking and eye symmetry on pupillary light reflex (PLR) parameters. METHODS: We evaluated 2812 eyes from 1406 subjects in a single-centre, cross-sectional study. PLR data were collected using four different stimulus intensities. We prepared two models for each of the eight PLR parameters, and defined the model with the lowest values of Akaike's information criterion (AIC) as being the best-fit. Model A was a linear regression model without adjustment for among-individual variability, while the Model B linear mixed-effects models (LMMs) were adjusted for among-individual variability. The regression coefficients of the two models were compared. RESULTS: Model B showed the lowest AIC values for all parameters and the best fit. For light stimulus intensity, age and eye symmetry, the two models yielded similar results for all PLR parameters. For sex and smoking index, some PLR parameters showed the opposite results, i.e., Model A showed significant effects while Model B did not. CONCLUSION: These results indicate that light stimulus intensity, aging, sex, smoking and eye symmetry are factors that affect PLR parameters. These should be adjusted when evaluating the clinical potential of PLR as a diagnostic tool. In addition, adjusting for among-individual variability due to LMMs can improve the model fit and reduce false positives. This can reveal the association between clinical factors and PLR parameters with increased accuracy.

Light stimulus responsive nanomedicine in the treatment of oral squamous cell carcinoma.

Light stimulus responsive therapies are based on a variety of low-toxic therapeutic agents and produce anti-tumor effects only under external light stimulation, thus greatly reducing system toxicity and improving the specificity of treatment. Moreover, light stimulus responsive drug delivery system (DDS) can combine various theranostics molecules to exert synergistic therapeutic effects of various treatments, which has played an important role in cancer treatment. In this review, we introduced the light stimulus responsive cancer therapies including photodynamic therapy (PDT), photothermal therapy (PTT) and light-triggered DDS applied in the treatment of OSCC, described considerable photosensitizers (PSs) and nanomaterials used for oral cancers, which will hope to better the clinic outcome of OSCC patients.

Gamma Band Light Stimulation in Human Case Studies: Groundwork for Potential Alzheimer's Disease Treatment.

BACKGROUND: It is known that proteins associated with Alzheimer's disease (AD) pathogenesis are significantly reduced by 40 Hz entrainment in mice. If this were to translate to humans, verifying that such a light stimulus can induce a 40 Hz entrainment response in humans and harnessing insights from these case studies could be one step in the development of a multisensory device to prevent and treat AD. OBJECTIVE: Verify the inducement of a 40 Hz response in the human brain by a 40 Hz light stimulus and obtain insights that could potentially aid in the development of a multisensory device for the prevention and treatment of AD. METHODS: Electroencephalographic brain activity was recorded simultaneously with application of stimulus at different frequencies and intensities. Power spectral densities were analyzed. RESULTS: Entrainment to visual stimuli occurred with the largest response at 40 Hz. The high intensity 40 Hz stimulus caused widespread entrainment. The number of electrodes demonstrating entrainment increased with increasing light intensity. Largest amplitudes for the high intensity 40 Hz stimulus were consistently found at the primary visual cortex. There was a harmonic effect at double the frequency for the 40 Hz stimulus. An eyes-open protocol caused more entrainment than an eyes-closed protocol. CONCLUSION: It was possible to induce widespread entrainment using a 40 Hz light stimulus in this sample cohort. Insights gleaned from these case studies could potentially aid in the development of a multisensory medical device to prevent and treat AD.

First report of luminous stimuli eliciting sound production in weevils.

Light-based stimuli elicited acoustic responses in male Hylesinus aculeatus Say (Curculionidae: Scolytinae: Hylesinina) instantaneously, with 100% reliability. Stridulations were elicited with a white light beam in a dark environment and recorded with an ultrasonic microphone. Acoustic responses were consistent, and, when compared with sounds produced under stressful conditions (i.e. physical stimulation), no significant differences were found. Hylesinus aculeatus possess an elytro-tergal stridulatory organ and acoustic communication is only present in males. This is also the first report of acoustic communication for this species. Instantaneous light-elicited acoustic communication has potential applications in the development of electronic traps and real-time acoustic detection and identification of beetles, border biosecurity, and noise-reduction in acoustic data collection.

[A light stimulation device and optical control experiment method for carp robots].

In order to solve the problems that the injury, hemorrhage, infection and edema of the brain tissue caused by brain electrodes implantation for aquatic animal robots, a light stimulation device and an optical control experiment method for carp robots are proposed in this paper. According to the shape of the carp skull, the device is a structure of Chinese character "" cut by a printed circuit board which can provide three groups of A, B and C bridge platforms for the light stimulation source. The two ends of a bridge in every group are welded with a jumper board, and the light emitting diodes (LED) are inserted into the jumper boards as the light stimulation source, and all negative poles of the jumper boards are connected to the console by the wire. A LED light can be replaced by another LED light according to the need of the wavelength of the LED light, and various combinations of the light stimulation modes can be also selected. This device was mounted on the carp robot's head, the carp robot was placed in a water maze, and the optical control experiment method was observed to control the forward movement and steering movement of the carp robots ( n = 10) under the dark light condition. The results showed that the success rates of the three groups of red light control experiments were 53%-87%, and the success rates of the three groups of blue light control experiments were 50%-80%. This study shows that the apparatus and the method are feasible.

Effects of maternal anxiety and depression on fetal neuro-development.

BACKGROUND: Fetal development is affected by maternal mental health with research indicating that maternal anxiety and depression are co-morbid; nevertheless differential effects on the fetus have been found. This study examines, prenatally, effects of maternal stress, anxiety and depression on fetal eye-blink reactions to experimental sound and light stimulation. METHODS: Two groups of singleton fetuses (mean 32-weeks gestation) were examined using 4D ultrasound: a control group (N = 14, 7 female) with no stimulation and an experimental group (N = 21, 13 female) exposed to experimental sound, light and cross-modal stimulation. For both groups ultrasound scans were performed and fetal eye-blink was assessed. Mothers completed the Hospital-Anxiety-and-Depression Scale and the Perceived-Stress Scale. Analysis was carried out using Poisson mixed effects modelling. RESULTS: Fetal eye-blink rate during experimental stimulation was significantly and differentially associated with maternal mental health with a 20% increase of fetal eye-blink rate for each unit increase in anxiety score (p = 0.02) and a decrease of 21% of eye blink rate for each unit of increase in depression score (p = 0.02). Sound stimulation but not light stimulation significantly affected blink-rate with fetuses habituating to the stimuli (p < 0.001). LIMITATIONS: Limitations are the relatively small number of fetuses and that a follow up after birth is essential to establish potential long-term effects. CONCLUSIONS: Of clinical importance is the finding that although fetuses are affected by maternal mental health in general here we demonstrate, using eye-blink-rate during stimulation as measure of neuro-development, that fetuses are differentially affected by maternal anxiety and depression with anxiety increasing and depression decreasing fetal reactivity significantly.

The impact factors in reward conditioned reflex test of rats / 中国比较医学杂志

Objective To study the effects of different color light stimulus, duration of stimulus and day/night training on the incentive conditioned reflex of rats,and to provide a data basis for the methodology of incentive conditional reflection experiments. Methods Three experiments were included in this study. During the experiment 1, a total of 30 male 8-week-old Wistar rats were divided into three groups:red light stimulation group,yellow light stimulation group and blue light stimulation group. During the experiment 2, a total of 32 male 8-week-old Wistar rats were divided into three groups:the group I(with a light stimulation duration of 10 s), the group II(with a light stimulation duration of 30 s), and the group III(with a light stimulation duration of 60 s). During the experiment 3,a total of 16 male 8-week-old Wistar rats were randomly divided into two groups,of which the first group was trained at 9:00 a.m. every day, and the second group was trained at 21:00 every day. All the laboratory animals were given reward conditioned reflex training, and indicators such as the number of correct nose pokes,the number of incorrect nose pokes,the ratio of correct nose pokes and so on were counted and calculated. Results During the experiment 1,there was no significant difference in the numbers of correct nose pokes and incorrect nose pokes,movement distances and average speeds of the rats among the three groups. During the experiment 2,compared with the group with a light duration of 10 s,the rats in the groups with a light duration of 30 s or 60 s had a higher number of correct nose pokes(P< 0.05). Moreover,on the 13th and 14th days,the ratio of correct nose pokes of the group with a light duration of 30 s was significantly higher than that of the group with a light duration of 10 s(P< 0.001). During the experiment 3,there were no significant differences in the number of correct nose pokes and the nose poke accuracy of the rats between the two groups. Conclusions In the reward conditioned reflex test, red,yellow and blue light stimuli have similar reward prediction effect. When stimulated with the same light, the time of stimulation has an impact on the learning ability of the rats,and an appropriate extension of stimulation is beneficial to the formation of conditioned reflex in them. The day/night training has no effect on the learning and memory ability of the rats.

A light stimulation device and optical control experiment method for carp robots / 生物医学工程学杂志

In order to solve the problems that the injury, hemorrhage, infection and edema of the brain tissue caused by brain electrodes implantation for aquatic animal robots, a light stimulation device and an optical control experiment method for carp robots are proposed in this paper. According to the shape of the carp skull, the device is a structure of Chinese character " cut by a printed circuit board which can provide three groups of A, B and C bridge platforms for the light stimulation source. The two ends of a bridge in every group are welded with a jumper board, and the light emitting diodes (LED) are inserted into the jumper boards as the light stimulation source, and all negative poles of the jumper boards are connected to the console by the wire. A LED light can be replaced by another LED light according to the need of the wavelength of the LED light, and various combinations of the light stimulation modes can be also selected. This device was mounted on the carp robot's head, the carp robot was placed in a water maze, and the optical control experiment method was observed to control the forward movement and steering movement of the carp robots ( = 10) under the dark light condition. The results showed that the success rates of the three groups of red light control experiments were 53%-87%, and the success rates of the three groups of blue light control experiments were 50%-80%. This study shows that the apparatus and the method are feasible.

Effect of ambient light on the time needed to complete a fetal biophysical profile: A randomized controlled trial.

OBJECTIVE: The objective of this study is to determine whether ambient light serves as a fetal stimulus to decrease the amount of time needed to complete a biophysical profile. STUDY DESIGN: This is a randomized controlled trial of singleton gestations undergoing a biophysical profile. Patients were randomized to either ambient light or a darkened room. The primary outcome was the time needed to complete the biophysical profile. Secondary outcomes included total and individual component biophysical profile scores and scores less than 8. A subgroup analysis of different maternal body mass indices was also performed. RESULTS: 357 biophysical profile studies were analyzed. 182 studies were performed with ambient light and 175 were performed in a darkened room. There was no difference in the median time needed to complete the biophysical profile based on exposure to ambient light (6.1min in darkened room versus 6.6min with ambient light; P=0.73). No difference was found in total or individual component biophysical profile scores. Subgroup analysis by maternal body mass index did not demonstrate shorter study times with ambient light exposure in women who were normal weight, overweight or obese. CONCLUSION: Ambient light exposure did not decrease the time needed to complete the biophysical profile. There was no evidence that ambient light altered fetal behavior observed during the biophysical profile.

Interactive Light Stimulus Generation with High Performance Real-Time Image Processing and Simple Scripting.

Light stimulation with precise and complex spatial and temporal modulation is demanded by a series of research fields like visual neuroscience, optogenetics, ophthalmology, and visual psychophysics. We developed a user-friendly and flexible stimulus generating framework (GEARS GPU-based Eye And Retina Stimulation Software), which offers access to GPU computing power, and allows interactive modification of stimulus parameters during experiments. Furthermore, it has built-in support for driving external equipment, as well as for synchronization tasks, via USB ports. The use of GEARS does not require elaborate programming skills. The necessary scripting is visually aided by an intuitive interface, while the details of the underlying software and hardware components remain hidden. Internally, the software is a C++/Python hybrid using OpenGL graphics. Computations are performed on the GPU, and are defined in the GLSL shading language. However, all GPU settings, including the GPU shader programs, are automatically generated by GEARS. This is configured through a method encountered in game programming, which allows high flexibility: stimuli are straightforwardly composed using a broad library of basic components. Stimulus rendering is implemented solely in C++, therefore intermediary libraries for interfacing could be omitted. This enables the program to perform computationally demanding tasks like en-masse random number generation or real-time image processing by local and global operations.

Integrated RNA-seq and sRNA-seq analysis reveals miRNA effects on secondary metabolism in Solanum tuberosum L.

Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenylpropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light-responsive miRNAs are important regulators in alkaloids metabolism, UMP salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of miRNA and mRNA expression profiles in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato.

Morphological plasticity of the clonal herb Lamiastrum galeobdolon (L.) Ehrend. & Polatschek in response to partial shading.

The present experiment investigates the morphological plasticity of Lamiastrum galeobdolon (L.) Ehrend. & Polatschek in response to light patchiness. In a garden experiment, stolons of the plant were grown under the following six light regimes: high light, low light, from low light to high light, from high light to low light, under high light but with the apical region of the stolon under low light, and under low light but with the apical region under high light. The low-light conditions provided 50% of high light PAR and 28% of high light R/FR ratio (ratio of red to far red light), and simulated the canopy-like shade that may be relevant to this species in its natural habitat. Plants growing under different light treatments did not show significant differences in total plant dry weight, total number of ramets, number of primary ramets, number of secondary ramets, and number of branches per clone. L. galeobdolon plants growing under high-light conditions formed shorter internodes, shorter petioles and smaller laminas with lower SLA, and showed higher branching intensity than those growing under low-light conditions. Accordingly, when growing between patches of different light conditions, the primary ramets had shorter internodes, shorter petioles and smaller laminas with lower SLA in high-light than in low-light patches. Exposing the apical region, of an otherwise shaded stolon, to high light shortened its internodes, compared with those of plants growing entirely under low-light conditions. Shading the apical region, of otherwise unshaded stolon, had no effect on the lengths of these internodes. In contrast, the morphology of the leaf responded to local light conditions only. Elongation of stolon internodes was completed much faster (within 2 or 3 wk) than lamina expansion and petiole extension, which took at least 6 wk. These results are interpreted in terms of the efficiency of exploitation of high-light patches within the habitat of L. galeobdolon.