Effects of Blindness on Sleep/Wakefulness States in Mice.

To examine the effects of blindness on sleep/wakefulness states, we compared locomotor activity and delayed recovery from isoflurane anesthesia induced by hypnotics during light and dark periods in sighted CBA/N and blind CBA/J mice. Locomotor activity around the switch from the dark to light period significantly differed in both mice. Delayed recovery induced by brotizolam was attenuated in both periods in CBA/J mice. In addition, the period specificity of delayed recovery caused by suvorexant or diphenhydramine in CBA/N mice was abolished in CBA/J mice. These results suggest that blindness impairs sleep quality.

Effects of cryopreservation on the mitochondrial bioenergetics of bovine sperm.

This study evaluated the bioenergetic map of mitochondria metabolism in cryopreserved bovine sperm. The detected oligomycin-sensitive basal respiration supported ATP production; frozen-thawed spermatozoa were found to have a coupling efficiency higher than 0.80. Cell respiration, however, was not stimulated by the protonophoric action of FCCP, as its titration with 1, 2, 4 and 6 µM did not stimulate the uncoupling activity on oxidative phosphorylation as highlighted by unresponsive oxygen consumption. The unusual effect on the stimulation of maximal respiration was not related to fibronectin- or PDL-coated plates used for cellular metabolism analysis. Conversely, irradiation of frozen-thawed bovine sperm with the red light improved mitochondrial parameters. In effect, the maximal respiration of red-light-stimulated sperm in PDL-coated plates was higher than the non-irradiated. In spite of this, red-light irradiation had no impact on membrane integrity and mitochondrial activity evaluated by epifluorescence microscopy.

Properties of a Symmetrical Photoacoustic Helmholtz Cell Operating with Imbalanced Counterphase Light Stimulation.

The output signal from a photoacoustic cell based on a symmetrical Helmholtz resonator structure can be substantially increased if a counterphase light stimulation is applied to the cell cavities. However even slight differences in the intensity of the light beams irradiating the cavities may affect the frequency response of the cell and the output signal level. This paper shows the influence of the imbalanced light irradiation on the properties of such a cell. It was found that even at relatively high irradiation mismatch, and even with the photoacoustic signal detection implemented with a single microphone, the influence of the irradiation imbalance on the frequency response of the cell around the resonance frequency is not critical. In the case of differential detection of the photoacoustic signal, the imbalance of the light irradiation does not affect the frequency response of the cell, but only the output signal level.

Effect of two constant light regimens on antibody profiles and immune gene expression in Atlantic salmon following vaccination and experimental challenge with salmonid alphavirus.

Before seawater transfer, farmed Atlantic salmon are subjected to treatments that may affect the immune system and susceptibility to pathogens. E.g., exposure to constant light (CL) stimulates smoltification, which prepares salmon to life in sea water, but endocrine changes in this period are associated with suppression of immune genes. Salmon are vaccinated towards end of the freshwater period to safeguard that adequate vaccine efficacy is achieved by the time the fish is transferred to sea. In the present study, we investigated how the responses to vaccination and viral infection varied depending on the time of CL onset relative to vaccination. The salmon were either exposed to CL two weeks prior to vaccination (2-PRI) or exposed to CL at the time of vaccination (0-PRI). A cohabitant challenge with salmonid alphavirus, the causative agent of pancreatic disease, was performed 9 weeks post vaccination. The immunological effects of the different light manipulation were examined at 0- and 6-weeks post vaccination, and 6 weeks post challenge. Antibody levels in serum were measured using a serological bead-based multiplex panel as well as ELISA, and 92 immune genes in heart and spleen were measured using an integrated fluidic circuit-based qPCR array for multiple gene expression. The 2-PRI group showed a moderate transcript down-regulation of genes in the heart at the time of vaccination, which were restored 6 weeks after vaccination (WPV). Conversely, at 6WPV a down-regulation was seen for the 0-PRI fish. Moreover, the 2-PRI group had significantly higher levels of antibodies binding to three of the vaccine components at 6WPV, compared to 0-PRI. In response to SAV challenge, transcription of immune genes between 2-PRI and 0-PRI was markedly dissimilar in the heart and spleen of control fish, but no difference was found between vaccinated salmon from the two CL regimens. Thus, by using labor-saving high throughput detection methods, we demonstrated that light regimens affected antibody production and transcription of immune genes in non-vaccinated and virus challenged salmon, but the differences between the light treatment groups appeared eliminated by vaccination.

Optogenetic neuronal stimulation promotes axon outgrowth and myelination of motor neurons in a three-dimensional motor neuron-Schwann cell coculture model on a microfluidic biochip.

Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron-Schwann cell (MN-SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs. Following coculture with SCs on the microfluidic biochip, MNs were transfected with a light-sensitive channelrhodopsin gene. Transfected MNs subjected to repeated light stimulation (20 Hz, 1 hr) produced significantly longer axons than nontransfected MNs. OMLS of MNs greatly increased the number of myelin basic protein (MBP)-expressing SCs, promoting the initiation of myelination of MNs. Ultrastructurally, OMLS of MNs markedly enhanced the thickness of the compact myelin sheath around the MN axons such that the average thickness was closer to that of the theoretical estimates in vivo. Thus, the MN-SC coculture model on a microfluidic biochip augmented by OMLS of MNs is a feasible platform for studying the relationship of neuronal activity with regrowth and remyelination.

Red-light stimulation of boar semen prior to artificial insemination improves field fertility in farms: A worldwide survey.

A survey of in vivo fertility data from 31 pig farms distributed worldwide was conducted to determine whether stimulating boar semen with LED-based red light increases its reproductive performance following artificial insemination (AI). Red-light stimulation with MaXipig® was found to increase farrowing rates (mean ± SEM, control: 87.2% ± 0.4% vs. light stimulation 90.3% ± 0.5%) and the number of both total and live newborn piglets. Red-light stimulation increased farrowing rates in 27 farms, with an increase ranging from 0.2% to 9.1%. Similar results were observed in litter sizes. Suboptimal management after AI was suggested in those farms with no response to red-light stimulation. Our results indicate that a routine use of red-light stimulation of boar semen can have a positive effect on the reproductive performance. However, the effectiveness of this system appears to highly rely upon proper management of pig farms.

Optogenetics, the intersection between physics and neuroscience: light stimulation of neurons in physiological conditions.

Neuronal stimulation by light is a novel approach in the emerging field of optogenetics, where genetic engineering is used to introduce light-activated channels. However, light is also capable of stimulating neurons even in the absence of genetic modifications through a range of physical and biological mechanisms. As a result, rigorous design of optogenetic experiments needs to take note of alternative and parallel effects of light illumination of neuronal tissues. Thus all matters relating to light penetration are critical to the development of studies using light-activated proteins. This paper discusses ways to quantify light, light penetration in tissue, as well as light stimulation of neurons in physiological conditions. We also describe the direct effect of light on neurons investigated at different sites.

The effect of acupressure and halogen light stimulation on nonstress testing and antenatal anxiety: A randomized controlled trial.

CONTEXT: Acupressure and halogen light stimulation, are used to reduce false non-reactive nonstress test results related to fetal sleep. OBJECTIVE: This study was conducted to determine the effect of acupressure and halogen light stimulation on nonstress testing and anxiety during pregnancy. DESIGN: Randomized controlled experimental study. SETTING: The population of the study consisted of pregnant women who were requested to have a nonstress test. PARTICIPANTS: The sample of the study included 132 pregnant women (acupressure group:44; halogen light group:45, and control group:43). METHODS: The acupressure group was applied acupressure on the Zhiyin acupuncture point three times, the halogen light group was applied halogen light stimulation twice on the fetal head from the mother's abdomen. In the interpretation of the results, the level of statistical significance was taken as P < 0.05. MAIN OUTCOME PARTICIPANTS: In our study, there was no difference between the acupressure and halogen light groups in terms of the mean number of fetal movements, the number of accelerations, the time to the first acceleration, and the time to reach the reactive result in the nonstress test (P > 0.05), while the mean number of fetal movements and accelerations of these two groups were higher, and the mean time to the first acceleration and the mean time to reach the reactive result in the nonstress test were shorter than those of the control group (P < 0.05). In addition, no statistically significant difference was found between the groups in terms of mean state anxiety inventory scores (P > 0.05). RESULTS: Acupressure and halogen light stimulation increased the rates of reactive nonstress tests.

Significance of homogeneous operation in light-assisted fixed-bed bioprocess under ammonia stress: Optimization, long-term operation and metagenomic analysis.

Activating microbes with light is a promising strategy for addressing ammonia-stressed anaerobic digestion (AD). However, as a critical in-process parameter, homogenous operation, in light-assisted AD amended by bio-fixed bed has received limited attention. This research endeavors to establish a uniform-illuminated biosystem and assess its practical feasibility through a 90-day semi-continuous operation at pilot scale under solar light illumination. With optimal stirring mode (intermittent stirring for 3 min every 15 min), robust methane yields were achieved across various organic loads, reaching 88.7-94.3% of theoretical yield under high ammonium stress (3500 mg/L). The metagenomic analysis unveiled that uniform illumination triggered synergistic effects in AD, fostering a diversified microbial consortium, enhancing carbohydrate and methane metabolism, and facilitating the formation of an electroactive bio-cluster. This study underscores the significance of homogenous illumination in AD systems for efficient waste-to-energy conversion, highlighting the implementation of solar light as a greener approach for scale-up application.

Flicker light stimulation enhances the emotional response to music: a comparison study to the effects of psychedelics.

Flicker light stimulation (FLS) is a non-pharmacological method of inducing altered states of consciousness (ASCs), producing hallucination-like phenomena as well as effects extending beyond the visual modality, including emotional effects. Research into the psychological and neural mechanisms of FLS is still in its infancy, but can be informed by research into other methods of inducing ASCs. For instance, research on classic psychedelics has reported enhancement of emotional responses to music. Here, we test to what degree FLS might also enhance the emotional response to music, using a study protocol designed to resemble a previous study on the effects of LSD as closely as possible, to allow for comparison of effect sizes across modalities and inform future research into FLS as an ASC-induction method. Twenty participants listened to emotionally evocative music in two conditions - with and without FLS - and reported on their emotional response to the music. FLS showed a significant enhancing effect on reported music-evoked emotion, especially emotions relating to "Joyful Activation"; additionally, we found that the experienced intensity of FLS correlated with reports of higher levels of emotional arousal. These findings motivate further research into FLS as a method for inducing ASCs and into the interactions between visual phenomena and music-evoked emotion.

Contributions of the light environment and co-sleeping to sleep consolidation into nighttime in early infants: A pilot study.

BACKGROUND: Sleep consolidation into nighttime is considered the primary goal of sleep development in early infants. However, factors contributing to sleep consolidation into nighttime remain unclear. AIM: To clarify the influences of the light environment and nighttime co-sleeping on sleep consolidation into nighttime in early infants. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Sleep-wake time and light stimulation were measured in infants for 4 consecutive days using actigraphy. The infants' mothers were asked to complete a sleep events diary and a questionnaire about childcare, including "co-sleeping", defined as when the infant and mother slept on the same surface throughout the night. OUTCOME MEASURES: The data were analyzed with a focus on daytime and nighttime sleep parameters. RESULTS: Daytime light stimulation reduced daytime "active sleep", tended to reduce daytime sleep, and increased daytime waking. Nighttime light stimulation reduced nighttime "quiet sleep" and nighttime sleep and increased nighttime waking. Co-sleeping reduced nighttime waking, and, as a result, nighttime sleep time and sleep efficiency increased. Co-sleeping reduced daytime sleep and tended to increase daytime waking. Consequently, co-sleeping tended to increase the ratio of nighttime sleep to daytime sleep. CONCLUSIONS: The present findings suggest that an appropriate light environment promotes daytime waking and nighttime sleep in early infants, but it does not contribute to sleep consolidation into nighttime by itself. On the other hand, co-sleeping may promote sleep consolidation into nighttime. Therefore, further methods for safe co-sleeping need to be established while avoiding risk factors for sudden unexpected death in infancy/sudden infant death syndrome.

Effects of angle of incidence of stimulus light on photopic electroretinograms of zebrafish larvae.

In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5-6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P < 0.0001 and P = 0.015, respectively). However, the difference between the b-wave amplitudes elicited at D30° and V30° stimuli were not significant (P = 0.98), and the d-wave amplitudes were also not significantly different (P = 0.20). The average b-wave amplitudes elicited at D30° stimulation was 84.6 ± 15.7% and V30° stimulation was 84.8 ± 17.4% relative to that of F0° stimulation. The average d-wave amplitudes elicited by D30° stimulation was 85.5 ± 15.2% and by V30° stimulation was 79.0 ± 11.0% relative to that of F0° stimulation. The differences in the implicit times of the b- and d-wave elicited by the different directions of stimulation were not significant (P = 0.52 and P = 0.14, respectively). We conclude that the amplitude of the photopic ERGs is affected by the angle of the incident light. Thus, it would be better to use ganzfeld stimuli to elicit maximum b- and d-wave amplitudes of the photopic ERGs of zebrafish larvae.

Sub-second timing irregularities in a simple motor task in autism spectrum disorder: Preliminary effects of intermittent light stimulation.

Several authors have contributed extensively to the neurocognitive understanding of timing. In Autism Spectrum Disorder (ASD) on the contrary, internal timing and its functioning is not well understood. In this study, we have adapted a simple finger-tapping motor task, with a timing component, as we aim at understanding whether the processing of time is preserved in this population. We have tested a group of people on the autism spectrum without intellectual disabilities and a control sample recruited from the general population, matched for age, sex, schooling and general cognitive abilities on this task with a learning and testing phase. In the testing phase, we have added two exploratory conditions where participants were exposed to intermittent light stimulation of 4 and 8 Hz. Results show that both in the learning and testing phase, besides troubles in the motor component encountered by the people on the spectrum, their timing component performance was also problematic. This reveals to be especially true for time intervals below the 1 s range, as hypothesized, whereas performance in longer intervals is clearly preserved. It was also observed that the exposure to intermittent light stimulation specifically overcomes the difficulties observed in the autistic group, at the timing components at this millisecond time range. The observed timing difficulties in this group seem to be restricted to the system responsible for the processing of time intervals in the milliseconds range, which helps accommodate disparate findings in the literature.

Cognitive Decline: Current Intervention Strategies and Integrative Therapeutic Approaches for Alzheimer's Disease.

Alzheimer's disease (AD) represents a pressing global health challenge, with an anticipated surge in diagnoses over the next two decades. This progressive neurodegenerative disorder unfolds gradually, with observable symptoms emerging after two decades of imperceptible brain changes. While traditional therapeutic approaches, such as medication and cognitive therapy, remain standard in AD management, their limitations prompt exploration into novel integrative therapeutic approaches. Recent advancements in AD research focus on entraining gamma waves through innovative methods, such as light flickering and electromagnetic fields (EMF) stimulation. Flickering light stimulation (FLS) at 40 Hz has demonstrated significant reductions in AD pathologies in both mice and humans, providing improved cognitive functioning. Additionally, recent experiments have demonstrated that APOE mutations in mouse models substantially reduce tau pathologies, with microglial modulation playing a crucial role. EMFs have also been demonstrated to modulate microglia. The exploration of EMFs as a therapeutic approach is gaining significance, as many recent studies have showcased their potential to influence microglial responses. Th article concludes by speculating on the future directions of AD research, emphasizing the importance of ongoing efforts in understanding the complexities of AD pathogenesis through a holistic approach and developing interventions that hold promise for improved patient outcomes.

Rationale and design of a double-blinded, randomized placebo-controlled trial of 40 Hz light neurostimulation therapy for depression (FELIX).

BACKGROUND: Major depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One of the potential biomarkers, gamma-frequency (30-80 Hz) brainwaves, are hypothesized to originate from the excitatory-inhibitory interaction between the pyramidal cells and interneurons. The imbalance between this interaction is described as a crucial pathological mechanism in neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. Previous studies attempted to induce gamma activity in the brain using rhythmic light and sound stimuli (GENUS - Gamma Entrainment Using Sensory stimuli) that resulted in neuroprotective effects in Alzheimer's disease (AD) patients and animal models. Here, we investigate the antidepressant, cognitive, and electrophysiological effects of the novel light therapy approach using 40 Hz masked flickering light for patients diagnosed with MDD. METHODS AND DESIGN: Sixty patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz masked flickering light stimulation while the control group will receive continuous light matched in color temperature and brightness. Patients in both groups will get daily light treatment in their own homes and will attend four follow-up visits to assess the symptoms of depression, including depression severity measured by Hamilton Depression Rating Scale (HAM-D17), cognitive function, quality of life and sleep, and electroencephalographic changes. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D6 subscale) between the groups.

Nanoparticles of Push-Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity.

Organic semiconductor materials with a unique set of properties are very attractive for interfacing biological objects and can be used for noninvasive therapy or detection of biological signals. Here, we describe the synthesis and investigation of a novel series of organic push-pull conjugated molecules with the star-shaped architecture, consisting of triphenylamine as a branching electron donor core linked through the thiophene π-spacer to electron-withdrawing alkyl-dicyanovinyl groups. The molecules could form stable aqueous dispersions of nanoparticles (NPs) without the addition of any surfactants or amphiphilic polymer matrixes with the average size distribution varying from 40 to 120 nm and absorption spectra very similar to those of human eye retina pigments such as rods and green cones. Variation of the terminal alkyl chain length of the molecules forming NPs from 1 to 12 carbon atoms was found to be an efficient tool to modulate their lipophilic and biological properties. Possibilities of using the NPs as light nanoactuators in biological systems or as artificial pigments for therapy of degenerative retinal diseases were studied both on the model planar bilayer lipid membranes and on the rat cortical neurons. In the planar bilayer system, the photodynamic activity of these NPs led to photoinactivation of ion channels formed by pentadecapeptide gramicidin A. Treatment of rat cortical neurons with the NPs caused depolarization of cell membranes upon light irradiation, which could also be due to the photodynamic activity of the NPs. The results of the work gave more insight into the mechanisms of light-controlled stimulation of neuronal activity and for the first time showed that fine-tuning of the lipophilic affinity of NPs based on organic conjugated molecules is of high importance for creating a bioelectronic interface for biomedical applications.

Multi-Stimuli-Responsive Tadpole-like Polymer/Lipid Janus Microrobots for Advanced Smart Material Applications.

Microrobots are of significant interest due to their smart transport capabilities, especially for precisely targeted delivery in dynamic environments (blood, cell membranes, tumor interstitial matrixes, blood-brain barrier, mucosa, and other body fluids). To perform a more complex micromanipulation in biological applications, it is highly desirable for microrobots to be stimulated with multiple stimuli rather than a single stimulus. Herein, the biodegradable and biocompatible smart micromotors with a Janus architecture consisting of PrecirolATO 5 and polycaprolactone compartments inspired by the anisotropic geometry of tadpoles and sperms are newly designed. These bioinspired micromotors combine the advantageous properties of polypyrrole nanoparticles (NPs), a high near-infrared light-absorbing agent with high photothermal conversion efficiency, and magnetic NPs, which respond to the magnetic field and exhibit multistimulus-responsive behavior. By combining both fields, we achieved an "on/off" propulsion mechanism that can enable us to overcome complex tasks and limitations in liquid environments and overcome the limitations encountered by single actuation applications. Moreover, the magnetic particles offer other functions such as removing organic pollutants via the Fenton reaction. Janus-structured motors provide a broad perspective not only for biosensing, optical detection, and on-chip separation applications but also for environmental water treatment due to the catalytic activities of multistimulus-responsive micromotors.

OptoPi: An open source flexible platform for the analysis of small animal behaviour.

Behaviour is the ultimate output of neural circuit computations, and therefore its analysis is a cornerstone of neuroscience research. However, every animal and experimental paradigm requires different illumination conditions to capture and, in some cases, manipulate specific behavioural features. This means that researchers often develop, from scratch, their own solutions and experimental set-ups. Here, we present OptoPi, an open source, affordable (∼ £600), behavioural arena with accompanying multi-animal tracking software. The system features highly customisable and reproducible visible and infrared illumination and allows for optogenetic stimulation. OptoPi acquires images using a Raspberry Pi camera, features motorised LED-based illumination, Arduino control, as well as irradiance monitoring to fine-tune illumination conditions with real time feedback. Our open-source software (BioImageProcessing) can be used to simultaneously track multiple unmarked animals both in on-line and off-line modes. We demonstrate the functionality of OptoPi by recording and tracking under different illumination conditions the spontaneous behaviour of larval zebrafish as well as adult Drosophila flies and their first instar larvae, an experimental animal that due to its small size and transparency has classically been hard to track. Further, we showcase OptoPi's optogenetic capabilities through a series of experiments using transgenic Drosophila larvae.

Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs.

Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools and human pluripotent stem cell differentiation models have the potential to fine-tune differentiation and unpick the processes by which cell specification and tissue patterning are controlled by morphogens. We used an optogenetic bone morphogenetic protein (BMP) signaling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs). We engineered light-sensitive hESCs through CRISPR-Cas9-mediated integration of the optoBMP system into the AAVS1 locus. The activation of optoBMP with blue light, in lieu of BMP growth factors, resulted in the activation of BMP signaling mechanisms and upregulation of a chondrogenic phenotype, with significant transcriptional differences compared to cells in the dark. Furthermore, cells differentiated with light could form chondrogenic pellets consisting of a hyaline-like cartilaginous matrix. Our findings indicate the applicability of optogenetics for understanding human development and tissue engineering.

Revisiting Transcranial Light Stimulation as a Stroke Therapeutic-Hurdles and Opportunities.

Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the end, we propose potential future opportunities with transcranial light stimulation as a cerebroprotective or restorative tool for future stroke treatment.