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The influences of UV light and integral light pulses from lamps on γ-irradiated LiF crystals with impurities of hydroxyl and magnesium ions have been investigated. The optical absorption and luminescence of color centers in different bleaching stages are studied depending on the crystal exposure time under UV light or on the number of light pulses. IR spectra of molecular hydrogen-bonded complexes and hydroxyl ions in different bleaching stages are presented. The transformation of strong hydrogen-bonded complexes under illumination into complexes with weak hydrogen bond (and vice versa) is studied. It is shown how molecular hydrogen-bonded complexes involving hydroxyl affect the transformation of color centers during the crystal bleaching. [ABSTRACT FROM AUTHOR]

In the area of laser material processing, versatile applications for cutting glasses and transparent polymers exist. However, parasitic effects such as the creation of step-like structures appear when laser cutting inside a transparent material. To date, these structures were only described empirically. This work establishes the physical and chemical mechanisms behind the observed effects and describes the influence of process and material parameters onto the creation of step-like structures in hydrogel, Dihydroxyethylmethacrylat (HEMA). By focusing laser pulses in HEMA, reduced pulse separation distance below 50 nm and rise in pulse energy enhances the creation of unintended step-like structures. Spatial resolved Raman-spectroscopy was used to measure the laser induced chemical modification, which results into a reduced breakdown threshold. The reduction in threshold influences the position of optical breakdown for the succeeding laser pulses and consequently leads to the step-like structures. Additionally, the experimental findings were supplemented with numerical simulations of the influence of reduced damage threshold onto the position of optical breakdown. In summary, chemical material change was defined as cause of the step-like structures. Furthermore, the parameters to avoid these structures were identified. [ABSTRACT FROM AUTHOR]

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this “presumably transient” dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock. [ABSTRACT FROM AUTHOR]

In this paper we consider the process of the second harmonic generation in a gradient waveguide, taking into account diffraction and relatively weak temporal dispersion. Using the slowly varying envelope approximation and neglecting the dispersion of the nonlinear part of the response of the medium we obtain the system of parabolic equations for the envelopes of both harmonics. We also derive integrals of motion of this system. To solve it numerically we construct a nonlinear finite-difference scheme based on the Crank-Nicolson method preserving the integrals. Primarily, we focus our investigations on the processes of a two-component light bullets generation. We demonstrate that the generation of a coupled pair is possible in a planar waveguide even at normal group velocity dispersion. [ABSTRACT FROM AUTHOR]

Ammonium pulse attributed to runoff of urban surface and agriculture following heavy rain is common in inland aquatic systems and can cause profoundly effects on the growth of macrophytes, especially when combined with low light. In this study, three patterns of NH4-N pulse (differing in magnitude and frequency) were applied to examine their effects on the growth of three submersed macrophytes, namely, Myriophyllum spicatum, Potamogeton maackianus, and Vallisneria natans, in terms of biomass, height, branch/ramet number, root length, leaf number, and total branch length under high and low light. Results showed that NH4-N pulse caused negative effects on the biomass of the submerged macrphytes even on the 13th day after releasing NH4-N pulse. The negative effects on M. spicatum were significantly greater than that on V. natans and P. maackianus. The effects of NH4-N pulse on specific species depended on the ammonium loading patterns. The negative effects of NH4-N pulse on P. maackianus were the strongest at high loading with low frequency, and on V. natans at moderate loading with moderate frequency. For M. spicatum, no significant differences were found among the three NH4-N pulse patterns. Low light availability did not significantly aggregate the negative effects of NH4-N pulse on the growth of the submersed macrophytes. Our study contributes to revealing the roles of NH4-N pulse on the growth of aquatic plants and its species specific effects on the dynamics of submerged macrophytes in lakes. [ABSTRACT FROM AUTHOR]

Red light promotes germination after activating phytochrome phyB, which destabilizes the germination repressor PIF1. Early upon seed imbibition, canopy light, unfavorable for photosynthesis, represses germination by stabilizing PIF1 after inactivating phyB. Paradoxically, later upon imbibition, canopy light stimulates germination after activating phytochrome phyA. phyA-mediated germination is poorly understood and, intriguingly, is inefficient, compared to phyB-mediated germination, raising the question of its physiological significance. A genetic screen identified polyamine uptake transporter 2 (put2) mutants that overaccumulate polyamines, a class of antioxidant polycations implicated in numerous cellular functions, which we found promote phyA-mediated germination. In WT seeds, our data suggest that canopy light represses polyamines accumulation through PIF1 while red light promotes polyamines accumulation. We show that canopy light also downregulates PIF1 levels, through phyA; however, PIF1 reaccumulates rapidly, which limits phyA-mediated germination. High polyamines levels in decaying seeds bypass PIF1 repression of germination and stimulate phyA-mediated germination, suggesting an adaptive mechanism promoting survival when viability is compromised. [ABSTRACT FROM AUTHOR]

Objective: Pulse transit time (PTT) refers to the time it takes a pulse wave to travel between two arterial sites. PTT can be estimated, amongst others, using the electrocardiogram (ECG) and photoplethysmogram (PPG). Because we observed a sawtooth artifact in the PTT while using standard patient monitoring equipment for ECG and PPG, we explored the reasons for this artifact. Methods: PPG and ECG were simulated at a heartrate of both 100 and 160 beats per minute while using a Masimo PPG post-processing module and a Philips patient monitor setup at the neonatal intensive care unit. Two different post-processing modules were used. PTT was defined as the difference between the R-peak in the ECG and the point of 50% increase in the PPG. Results: A sawtooth artifact was seen in all simulations. Both length (59.2 to 72.4 s) and amplitude (30.8 to 36.0 ms) of the sawtooth were dependent on the post-processing module used. Furthermore, the absolute PTT value differed up to 250 ms depending on post-processing module and heart rate. The sawtooth occurred because the PPG wave continuously showed a minimal prolongation during the length of the sawtooth, followed by a sudden shortening. Both artifacts were generated in the post-processing module containing Masimo algorithms. Conclusion: Post-processing of the PPG signal in the Masimo module of the Philips patient monitor introduces a sawtooth in PPG and derived PTT. This sawtooth, together with a large module-dependent absolute difference in PTT, renders the thus-derived PTT insufficient for clinical purposes. [ABSTRACT FROM AUTHOR]

In a Quantum Walk (QW) the “walker” follows all possible paths at once through the principle of quantum superposition, differentiating itself from classical random walks where one random path is taken at a time. This facilitates the searching of problem solution spaces faster than with classical random walks, and holds promise for advances in dynamical quantum simulation, biological process modelling and quantum computation. Here we employ a versatile and scalable resonator configuration to realise quantum walks with bright classical light. We experimentally demonstrate the versatility of our approach by implementing a variety of QWs, all with the same experimental platform, while the use of a resonator allows for an arbitrary number of steps without scaling the number of optics. This paves the way for future QW implementations with spatial modes of light in free-space that are both versatile and scalable. [ABSTRACT FROM AUTHOR]

While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a “rod-only” mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals. [ABSTRACT FROM AUTHOR]

Negative feedback loops (NFLs) for circadian clocks include light-responsive reactions that allow the clocks to shift their phase depending on the timing of light signals. Phase response curves (PRCs) for light signals in various organisms include a time interval called a dead zone where light signals cause no phase shift during daytime. Although the importance of the dead zone for robust light entrainment is known, how the dead zone arises from the biochemical reactions in an NFL underlying circadian gene expression rhythms remains unclear. In addition, the observation that the light-responsive reactions in the NFL vary between organisms raises the question as to whether the mechanism for dead zone formation is common or distinct between different organisms. Here we reveal by mathematical modeling that the saturation of a biochemical reaction in repressor synthesis in an NFL is a common mechanism of daytime dead zone generation. If light signals increase the degradation of a repressor protein, as in Drosophila, the saturation of repressor mRNA transcription nullifies the effect of light signals, generating a dead zone. In contrast, if light signals induce the transcription of repressor mRNA, as in mammals, the saturation of repressor translation can generate a dead zone by cancelling the influence of excess amount of mRNA induced by light signals. Each of these saturated reactions is located next to the light-responsive reaction in the NFL, suggesting a design principle for daytime dead zone generation. [ABSTRACT FROM AUTHOR]

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy has been largely neglected. During early life, most sensory systems are still largely immature. As a notable exception, the olfactory system is functional at birth, controlling mother–offspring interactions and neonatal survival. Here, we elucidate the structural and functional principles underlying the communication between olfactory bulb (OB) and lateral entorhinal cortex (LEC)—the gatekeeper of limbic circuitry—during neonatal development. Combining optogenetics, pharmacology, and electrophysiology in vivo with axonal tracing, we show that mitral cell–dependent discontinuous theta bursts in OB drive network oscillations and time the firing in LEC of anesthetized mice via axonal projections confined to upper cortical layers. Acute pharmacological silencing of OB activity diminishes entorhinal oscillations, whereas odor exposure boosts OB–entorhinal coupling at fast frequencies. Chronic impairment of olfactory sensory neurons disrupts OB–entorhinal activity. Thus, OB activity shapes the maturation of entorhinal circuits. [ABSTRACT FROM AUTHOR]

Heterokont algae are significant contributors to marine primary productivity. These algae have a photosynthetic machinery that shares many common features with that of Viridiplantae (green algae and land plants). Here we demonstrate, however, that the photosynthetic machinery of heterokont algae responds to light fundamentally differently than that of Viridiplantae. While exposure to high light leads to electron accumulation within the photosynthetic electron transport chain in Viridiplantae, this is not the case in heterokont algae. We use this insight to manipulate the photosynthetic electron transport chain and demonstrate that heterokont algae can dynamically distribute excitation energy between the two types of photosystems. We suggest that the reported electron transport and excitation distribution features are adaptations to the marine light environment. [ABSTRACT FROM AUTHOR]

Loss of one sensory modality can cause other types to become more perceptive (cross-modal plasticity). To test the hypothesis that the loss of vision changes the perceptual threshold in the somatosensory system, we applied optogenetics to directly manipulate the afferent inputs involved in the whisker-barrel system using a transgenic rat (W-TChR2V4) that expresses channelrhodopsin-2 (ChR2) selectively in the large mechanoreceptive neurons in the trigeminal ganglion (TG) and their peripheral nerve terminals. The licking behavior of W-TChR2V4 rat was conditioned to a blue LED light cue on the whisker area while the magnitude and duration of light pulses were varied. The perceptual threshold was thus quantitatively determined for each rat according to the relationship between the magnitude/duration of light and the reaction time between the LED light cue and the first licking event after it. We found that the perceptual threshold was more significantly reduced than the control non-deprived rats when the rats were visually deprived at postnatal 26–30 days (P26-30, early VD group), but not at P58-66 (late VD group). However, the sensory threshold of a late VD animal was similar to that of a control. Our results suggest the presence of cross-modal plasticity by which the loss of vision at the juvenile period increased the sensitivity of the somatosensory system involved in the touch of whiskers. [ABSTRACT FROM AUTHOR]

Many pharmaceuticals have negative effects on biota when released into the environment. For example, recent work has shown that the commonly prescribed antidiabetic drug, metformin (N,N-dimethylbiguanide), has endocrine disrupting effects on fish. However, effects of metformin on aquatic primary producers are poorly known. We exposed cultured isolates of a freshwater chlorophyte, Chlorella vulgaris, to a range of metformin concentrations (0–767.9 mg L-1) to test the hypothesis that exposure negatively affects photosynthesis and growth. A cessation of growth, increase in non-photochemical quenching (NPQ, NPQmax), and reduced electron transport rate (ETR) were observed 24 h after exposure to a metformin concentration of 767.8 mg L-1 (4.6 mM). By 48 h, photosynthetic efficiency of photosystem II (Fv/Fm), α, the initial slope of the ETR-irradiance curve, and Ek (minimum irradiance required to saturate photosynthesis) were reduced. At a lower concentration (76.8 mg L-1), negative effects on photosynthesis (increase in NPQ, decrease in ETR) were delayed, occurring between 72 and 96 h. No negative effects on photosynthesis were observed at an exposure concentration of 1.5 mg L-1. It is likely that metformin impairs photosynthesis either through downstream effects from inhibition of complex I of the electron transport chain or via activation of the enzyme, SnRK1 (sucrose non-fermenting-related kinase 1), which acts as a cellular energy regulator in plants and algae and is an ortholog of the mammalian target of metformin, AMPK (5' adenosine monophosphate-activated protein kinase). [ABSTRACT FROM AUTHOR]

Research in photobiology is currently limited by a lack of devices capable of delivering precise and tunable irradiation to cells in a high-throughput format. This limits researchers to using expensive commercially available or custom-built light sources which make it difficult to replicate, standardize, optimize, and scale experiments. Here we present an open-source Microplate Photoirradiation System (MPS) developed to enable high-throughput light experiments in standard 96 and 24-well microplates for a variety of applications in photobiology research. This open-source system features 96 independently controlled LEDs (4 LEDs per well in 24-well), Wi-Fi connected control and programmable graphical user interface (GUI) for control and programming, automated calibration GUI, and modular control and LED boards for maximum flexibility. A web-based GUI generates light program files containing irradiation parameters for groups of LEDs. These parameters are then uploaded wirelessly, stored and used on the MPS to run photoirradiation experiments inside any incubator. A rapid and semi-quantitative porphyrin metabolism assay was also developed to validate the system in wild-type fibroblasts. Protoporphyrin IX (PpIX) fluorescence accumulation was induced by incubation with 5-aminolevulinic acid (ALA), a photosensitization method leveraged clinically to destroy malignant cell types in a process termed photodynamic therapy (PDT), and cells were irradiated with 405nm light with varying irradiance, duration and pulsation parameters. Immediately after light treatment with the MPS, subsequent photobleaching was measured in live, adherent cells in both 96-well and a 24-well microplates using a microplate reader. Results demonstrate the utility and reliability of the Microplate Photoirradiation System to irradiate cells with precise irradiance and timing parameters in order to measure PpIx photobleaching kinetics in live adherent cells and perform comparable experiments with both 24 and 96 well microplate formats. The high-throughput capability of the MPS enabled measurement of enough irradiance conditions in a single microplate to fit PpIX fluorescence to a bioexponential decay model of photobleaching, as well as reveal a dependency of photobleaching on duty-cycle—but not frequency—in a pulsed irradiance regimen. [ABSTRACT FROM AUTHOR]

Drosophila retinal degeneration C (RDGC) is the founding member of the PPEF family of protein phosphatases. RDGC mediates dephosphorylation of the visual pigment rhodopsin and the TRP ion channel. From the rdgC locus, three protein isoforms, termed RDGC-S, -M, and -L, with different N-termini are generated. Due to fatty acylation, RDGC-M and -L are attached to the plasma membrane while RDGC-S is soluble. To assign physiological roles to these RDGC isoforms, we constructed flies that express various combinations of RDGC protein isoforms. Expression of the RDGC-L isoform alone did not fully prevent rhodopsin hyperphosphorylation and resulted in impaired photoreceptor physiology and in decelerated TRP dephosphorylation at Ser936. However, expression of RDGC-L alone as well as RDGC-S/M was sufficient to prevent degeneration of photoreceptor cells which is a hallmark of the rdgC null mutant. Membrane-attached RDGC-M displayed higher activity of TRP dephosphorylation than the soluble isoform RDGC-S. Taken together, in vivo activities of RDGC splice variants are controlled by their N-termini. [ABSTRACT FROM AUTHOR]

This study investigated the utility of the pupillary light reflex as a method of differentiating DSPD patients with delayed melatonin timing relative to desired/required sleep time (circadian type) and those with non-delayed melatonin timing (non-circadian type). All participants were young adults, with a total of 14 circadian DSPD patients (M = 28.14, SD = 5.26), 12 non-circadian DSPD patients (M = 29.42, SD = 11.51) and 51 healthy controls (M = 21.47 SD = 3.16) completing the protocol. All participants were free of central nervous system acting medications and abstained from caffeine and alcohol on the day of the assessment. Two pupillary light reflex measurements were completed by each participant, one with a 1s dim (~10 lux) light exposure, and one with a 1s bright (~1500 lux) light exposure. Circadian DSPD patients showed a significantly faster pupillary light reflex than both non-circadian DSPD patients and healthy controls. Non-circadian patients and healthy controls did not differ significantly. Receiver operating characteristic curves were generated to determine the utility of mean and maximum constriction velocity in differentiating the two DSPD phenotypes, and these demonstrated high levels of sensitivity (69.23–-100%) and specificity (66.67–91.67%) at their optimal cut offs. The strongest predictor of DSPD phenotype was the mean constriction velocity to bright light (AUC = 0.87). These results support the potential for the pupillary light reflex to clinically differentiate between DSPD patients with normal vs. delayed circadian timing relative to desired bedtime, without the need for costly and time-consuming circadian assessments. [ABSTRACT FROM AUTHOR]

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, iPPG) allow non-contact estimation of heart rate by its proxy, pulse rate. Yet, there is no established simple and non-invasive technique for pulse rate measurements in awake and behaving animals. Using iPPG, we here demonstrate that pulse rate in rhesus monkeys can be accurately estimated from facial videos. We computed iPPGs from eight color facial videos of four awake head-stabilized rhesus monkeys. Pulse rate estimated from iPPGs was in good agreement with reference data from a contact pulse-oximeter: the error of pulse rate estimation was below 5% of the individual average pulse rate in 83% of the epochs; the error was below 10% for 98% of the epochs. We conclude that iPPG allows non-invasive and non-contact estimation of pulse rate in non-human primates, which is useful for physiological studies and can be used toward welfare-assessment of non-human primates in research. [ABSTRACT FROM AUTHOR]

Cellular morphology and associated morphodynamics are widely used for qualitative and quantitative assessments of cell state. Here we implement a framework to profile cellular morphodynamics based on an adaptive decomposition of local cell boundary motion into instantaneous frequency spectra defined by the Hilbert-Huang transform (HHT). Our approach revealed that spontaneously migrating cells with approximately homogeneous molecular makeup show remarkably consistent instantaneous frequency distributions, though they have markedly heterogeneous mobility. Distinctions in cell edge motion between these cells are captured predominantly by differences in the magnitude of the frequencies. We found that acute photo-inhibition of Vav2 guanine exchange factor, an activator of the Rho family of signaling proteins coordinating cell motility, produces significant shifts in the frequency distribution, but does not affect frequency magnitude. We therefore concluded that the frequency spectrum encodes the wiring of the molecular circuitry that regulates cell boundary movements, whereas the magnitude captures the activation level of the circuitry. We also used HHT spectra as multi-scale spatiotemporal features in statistical region merging to identify subcellular regions of distinct motion behavior. In line with our conclusion that different HHT spectra relate to different signaling regimes, we found that subcellular regions with different morphodynamics indeed exhibit distinct Rac1 activities. This algorithm thus can serve as an accurate and sensitive classifier of cellular morphodynamics to pinpoint spatial and temporal boundaries between signaling regimes. [ABSTRACT FROM AUTHOR]

Bioluminescence is a fascinating phenomenon and can be found in many different organisms including fish. It has been suggested that bioluminescence is used for example for defense, prey attraction, and for intraspecific communication to attract for example sexual partners. The flashlight fish, Anomalops katoptron (A. katoptron), is a nocturnal fish that produces bioluminescence and lives in shallow waters, which makes it ideal for laboratory studies. In order to understand A. katoptron’s ability to detect bioluminescent light (480 to 490 nm) at night, we characterized the visual system adaptation of A. katoptron using phylogenetic, electrophysiological and behavioral studies. We found that the retinae of A. katoptron contain rods and sparse cones. A. katoptron retinae express two main visual pigments, rhodopsin (RH1), and to a lesser extent, rhodopsin-like opsin (RH2). Interestingly, recombinant RH1 and RH2 are maximally sensitive to a wavelength of approximately 490 nm light (λmax), which correspond to the spectral peak of in vivo electroretinogram (ERG) measurements. In addition, behavioral assays revealed that A. katoptron is attracted by low intensity blue but not red light. Collectively, our results suggest that the A. katoptron visual system is optimized to detect blue light in the frequency range of its own bioluminescence and residual starlight. [ABSTRACT FROM AUTHOR]

Optogenetics offers a unique method to regulate the activity of select neural circuits. However, the electrophysiological consequences of targeted optogenetic manipulation upon the entire circuit remain poorly understood. Analysis of the sensory-CNS-motor circuit in Drosophila larvae expressing eHpHR and ChR2-XXL revealed unexpected patterns of excitability. Optical stimulation of motor neurons targeted to express eNpHR resulted in inhibition followed by excitation of body wall contraction with repetitive stimulation in intact larvae. In situ preparations with direct electrophysiological measures showed an increased responsiveness to excitatory synaptic activity induced by sensory stimulation within a functional neural circuit. To ensure proper function of eNpHR and ChR2-XXL they were expressed in body wall muscle and direct electrophysiological measurements were obtained. Under eNpHR induced hyperpolarization the muscle remained excitable with increased amplitude of excitatory postsynaptic synaptic potentials. Theoretical models to explain the observations are presented. This study aids in increasing the understanding of the varied possible influences with light activated proteins within intact neural circuits. [ABSTRACT FROM AUTHOR]

The use of remote sensing techniques allows monitoring of photosynthesis at the ecosystem level and improves our knowledge of plant primary productivity. The main objective of the current study was to develop a remote sensing based method to measure microphytobenthos (MPB) primary production from intertidal mudflats. This was achieved by coupling hyperspectral radiometry (reflectance, ρ and second derivative, δδ) and PAM-fluorometry (non-sequential light curves, NSLC) measurements. The latter allowed the estimation of primary production using a light use efficiency parameter (LUE) and electron transport rates (ETR) whereas ρ allowed to estimate pigment composition and optical absorption cross-section (a*). Five MPB species representative of the main growth forms: epipelic (benthic motile), epipsammic (benthic motile and non motile) and tychoplanktonic (temporarily resuspended in the water column) were submitted to increasing light intensities from dark to 1950 μmol photons.m-2.s-1. Different fluorescence patterns were observed for the three growth-forms and were linked to their xanthophyll cycle (de-epoxydation state). After spectral reflectance measurements, a* was retrieved using a radiative transfer model and several radiometric indices were tested for their capacity to predict LUE and ETR measured by PAM-fluorometry. Only one radiometric index was not species or growth-form specific, i.e. δδ496/508. This index was named MPBLUE and could be used to predict LUE and ETR. The applicability of this index was tested with simulated bands of a wide variety of hyperspectral sensors at spectral resolutions between 3 and 15 nm of Full Width at Half Maximum (FWHM). [ABSTRACT FROM AUTHOR]

The circuit organization within the mammalian brainstem respiratory network, specifically within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes, and the roles of these circuits in respiratory pattern generation are continuously debated. We address these issues with a combination of optogenetic experiments and modeling studies. We used transgenic mice expressing channelrhodopsin-2 under the VGAT-promoter to investigate perturbations of respiratory circuit activity by site-specific photostimulation of inhibitory neurons within the pre-BötC or BötC. The stimulation effects were dependent on the intensity and phase of the photostimulation. Specifically: (1) Low intensity (≤ 1.0 mW) pulses delivered to the pre-BötC during inspiration did not terminate activity, whereas stronger stimulations (≥ 2.0 mW) terminated inspiration. (2) When the pre-BötC stimulation ended in or was applied during expiration, rebound activation of inspiration occurred after a fixed latency. (3) Relatively weak sustained stimulation (20 Hz, 0.5–2.0 mW) of pre-BötC inhibitory neurons increased respiratory frequency, while a further increase of stimulus intensity (> 3.0 mW) reduced frequency and finally (≥ 5.0 mW) terminated respiratory oscillations. (4) Single pulses (0.2–5.0 s) applied to the BötC inhibited rhythmic activity for the duration of the stimulation. (5) Sustained stimulation (20 Hz, 0.5–3.0 mW) of the BötC reduced respiratory frequency and finally led to apnea. We have revised our computational model of pre-BötC and BötC microcircuits by incorporating an additional population of post-inspiratory inhibitory neurons in the pre-BötC that interacts with other neurons in the network. This model was able to reproduce the above experimental findings as well as previously published results of optogenetic activation of pre-BötC or BötC neurons obtained by other laboratories. The proposed organization of pre-BötC and BötC circuits leads to testable predictions about their specific roles in respiratory pattern generation and provides important insights into key circuit interactions operating within brainstem respiratory networks. [ABSTRACT FROM AUTHOR]

We discuss a novel type of surface soliton—aberrated surface soliton—appearance in a nonlinear one dimensional photonic crystal and a possibility of this surface soliton formation in two dimensional photonic crystal. An aberrated surface soliton possesses a nonlinear distribution of the wavefront. We show that, in one dimensional photonic crystal, the surface soliton is formed at the photonic crystal boundary with the ambient medium. Essentially, that it occupies several layers at the photonic crystal boundary and penetrates into the ambient medium at a distance also equal to several layers, so that one can infer about light energy localization at the lateral surface of the photonic crystal. In the one dimensional case, the surface soliton is formed from an earlier formed soliton that falls along the photonic crystal layers at an angle which differs slightly from the normal to the photonic crystal face. In the two dimensional case, the soliton can appear if an incident Gaussian beam falls on the photonic crystal face. The influence of laser radiation parameters, optical properties of photonic crystal layers and ambient medium on the one dimensional surface soliton formation is investigated. We also discuss the influence of two dimensional photonic crystal configuration on light energy localization near the photonic crystal surface. It is important that aberrated surface solitons can be created at relatively low laser pulse intensity and for close values of alternating layers dielectric permittivity which allows their experimental observation. [ABSTRACT FROM AUTHOR]

Circadian clocks are ubiquitous in eukaryotic organisms where they are used to anticipate regularly occurring diurnal and seasonal environmental changes. Nevertheless, little is known regarding pathways connecting the core clock to its output pathways. Here, we report that the HAD family phosphatase CSP-6 is required for overt circadian clock output but not for the core oscillation. The loss of function Δcsp-6 deletion mutant is overtly arrhythmic on race tubes under free running conditions; however, reporter assays confirm that the FREQUENCY-WHITE COLLAR COMPLEX core circadian oscillator is functional, indicating a discrete block between oscillator and output. CSP-6 physically interacts with WHI-2, Δwhi-2 mutant phenotypes resemble Δcsp-6, and the CSP-6/WHI-2 complex physically interacts with WC-1, all suggesting that WC-1 is a direct target for CSP-6/WHI-2-mediated dephosphorylation and consistent with observed WC-1 hyperphosphorylation in Δcsp-6. To identify the source of the block to output, known clock-controlled transcription factors were screened for rhythmicity in Δcsp-6, identifying loss of circadian control of ADV-1, a direct target of WC-1, as responsible for the loss of overt rhythmicity. The CSP-6/WHI-2 complex thus participates in the clock output pathway by regulating WC-1 phosphorylation to promote proper transcriptional/translational activation of adv-1/ADV-1; these data establish an unexpected essential role for post-translational modification parallel to circadian transcriptional regulation in the early steps of circadian output. [ABSTRACT FROM AUTHOR]

Germination tests were performed on chickpeas, broad beans and green lentils, with the aim of identifying the processing conditions that allow improving germination efficiency and bioactivity profile of the germinated pulses. Germination experiments were carried out under different lighting conditions. The preliminary treatment of the soaked pulses through pulsed light of different fluency values before germination was also tested. Regardless of the investigated pulses, the dark or light regime had no significant influence on the total germination efficiency. Anyway, the light had a positive effect on the germination rate of chickpeas in the first 24 hours. A more pronounced increase of the antioxidant capacity was observed for samples germinated under dark conditions. The investigated pulses reacted differently to the pulsed light stimuli. Only in the case of lentils an increase of the percentage of germinated seeds was observed after the pulsed light treatment. Regarding the synthesis of both proteins and antioxidant compounds, the most promising results were registered for germinated broad beans after the pulsed light treatment at fluence of 43.2 J/cm². [ABSTRACT FROM AUTHOR]

The rodent whisker-barrel cortical system is a model for studying somatosensory discrimination at high spatiotemporal precision. Here, we applied optogenetics to produce somatosensory inputs in the whisker area using one of transgenic rat lines, W-TChR2V4, which expresses channelrhodopsin-2 (ChR2) in the mechanoreceptive nerve endings around whisker follicles. An awake W-TChR2V4 rat was head-fixed and irradiated by blue LED light on the whisker area with a paradigm conditioned with a reward. The Go task was designed so the rat is allowed to receive a reward, when it licked the nozzle within 5 s after photostimulation. The No-go task was designed so as the rat has to withhold licking for at least 5 s to obtain a reward after photostimulation. The Go-task conditioning was established within 1 hr of training with a reduction in the reaction time and increase of the success rate. To investigate the relationship between the spatiotemporal pattern of sensory inputs and the behavioral output, we designed a multi-optical fiber system that irradiates the whisker area at 9 spots in a 3×3 matrix. Although the Go-task conditioning was established using synchronous irradiation of 9 spots, the success rate was decreased with an increase of the reaction time for the asynchronous irradiation. After conditioning to the Go task, the rat responded to the blue LED flash irradiated on the barrel cortex, where many neurons also express ChR2, or photostimulation of the contralateral whisker area with a similar reaction time and success rate. Synchronous activation of the peripheral mechanoreceptive nerves is suggested to drive a neural circuit in the somatosensory cortex that efficiently couples with the decision. Our optogenetic system would enable the precise evaluation of the psychophysical values, such as the reaction time and success rate, to gain some insight into the brain mechanisms underlying conditioned behaviors. [ABSTRACT FROM AUTHOR]

The two sister peptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) and their receptors, the PAC1 –and the VPAC2 receptors, are involved in regulation of the circadian timing system. PACAP as a neurotransmitter in the retinohypothalamic tract (RHT) and VIP as a neurotransmitter, involved in synchronization of SCN neurons. Behavior and physiology in VPAC2 deficient mice are strongly regulated by light most likely as a result of masking. Consequently, we used VPAC2 and PAC1/VPAC2 double mutant mice in comparison with PAC1 receptor deficient mice to further elucidate the role of PACAP in the light mediated regulation of behavior and physiology of the circadian system. We compared circadian rhythms in mice equipped with running wheels or implanted radio-transmitter measuring core body temperature kept in a full photoperiod ((FPP)(12:12 h light dark-cycles (LD)) and skeleton photo periods (SPP) at high and low light intensity. Furthermore, we examined the expression of PAC1- and VPAC2 receptors in the SCN of the different genotypes in combination with visualization of PACAP and VIP and determined whether compensatory changes in peptide and/or receptor expression in the reciprocal knockouts (KO) (PAC1 and VPAC2) had occurred. Our data demonstrate that in although being closely related at both ligand and receptor structure/sequence, PACAP/PAC1 receptor signaling are independent of VIP/VPAC2 receptor signaling and vice versa. Furthermore, lack of either of the receptors does not result in compensatory changes at neither the physiological or anatomical level. PACAP/PAC1 signaling is important for light regulated behavior, VIP/VPAC2signaling for stable clock function and both signaling pathways may play a role in shaping diurnality versus nocturnality. [ABSTRACT FROM AUTHOR]

Neuronal cells receive a variety of excitatory and inhibitory signals which they process to generate an output signal. In order to study the interaction between excitatory and inhibitory receptors with exogenously applied transmitters in the same preparation, two caging chromophores attached to glutamate and GABA were developed that were selectively photolyzed by different wavelengths of light. This technique has the advantage that the biologically inactive caged compound can be applied at equilibrium prior to the near instantaneous release of the transmitters. This method therefore mimics the kinetics of endogenously released transmitters that is otherwise not possible in brain slice preparations. Repeated photolysis with either of the two wavelengths resulted in GABA- or glutamate-induced activation of both ionotropic and metabotropic receptors to evoke reproducible currents. With these compounds, the interaction between inhibitory and excitatory receptors was examined using whole field photolysis. [ABSTRACT FROM AUTHOR]

Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorption properties of GNRs following primary laser irradiation. [ABSTRACT FROM AUTHOR]

The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has also been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for euthanasia. However, correct interpretation of bioluminescent data is limited: the bioluminescence is different from gene expression because of nonlinear molecular and enzyme dynamics of the Lux system. We have developed a computational approach that, for the first time, allows users of Lux assays to infer gene transcription levels from the light output. This approach is based upon a new mathematical model for Lux activity, that includes the actions of LuxAB, LuxEC and Fre, with improved mechanisms for all reactions, as well as synthesis and turn-over of Lux proteins. The model is calibrated with new experimental data for the LuxAB and Fre reactions from Photorhabdus luminescens—the source of modern Lux reporters—while literature data has been used for LuxEC. Importantly, the data show clear evidence for previously unreported product inhibition for the LuxAB reaction. Model simulations show that predicted bioluminescent profiles can be very different from changes in gene expression, with transient peaks of light output, very similar to light output seen in some experimental data sets. By incorporating the calibrated model into a Bayesian inference scheme, we can reverse engineer promoter activity from the bioluminescence. We show examples where a decrease in bioluminescence would be better interpreted as a switching off of the promoter, or where an increase in bioluminescence would be better interpreted as a longer period of gene expression. This approach could benefit all users of Lux technology. [ABSTRACT FROM AUTHOR]

The hippocampus is the main locus of episodic memory formation and the neurons there encode the spatial map of the environment. Hippocampal place cells represent location, but their role in the learning of preferential location remains unclear. The hippocampus may encode locations independently from the stimuli and events that are associated with these locations. We have discovered a unique population code for the experience-dependent value of the context. The degree of reward-driven navigation preference highly correlates with the spatial distribution of the place fields recorded in the CA1 region of the hippocampus. We show place field clustering towards rewarded locations. Optogenetic manipulation of the ventral tegmental area demonstrates that the experience-dependent place field assembly distribution is directed by tegmental dopaminergic activity. The ability of the place cells to remap parallels the acquisition of reward context. Our findings present key evidence that the hippocampal neurons are not merely mapping the static environment but also store the concurrent context reward value, enabling episodic memory for past experience to support future adaptive behavior. [ABSTRACT FROM AUTHOR]

The locomotor activity rhythm of the sandhopperTalitrus saltator(Amphipoda Talitridae) was investigated in Madfoun beach. The rhythm was monitored in individual and group animals during 21 days at constant temperature. During the first two weeks, animals were kept under light–dark cycle (d1–d7) and constant darkness (d8–d14). Light pulses of 2 h were applied, at the end of the experimental night, during the first 3 days of the third week (d15–d18). Then, constant darkness was restored for the rest of the experiment (d19–d21). Results revealed thatTalitrus saltatorindividuals as well as groups concentrated their activities in experimental night under light–dark cycle and in the presence of pulses; whereas, a clear drift of activity is observed under constant darkness. Periodogram analysis showed the presence of circadian component whatever the recording type. An ultradian period was revealed in individual recording whatever the regimen, while for groups, this component appeared only under nLD cycle. Furthermore, the locomotor rhythm is more defined under nLD cycle for individuals and in constant darkness for groups. [ABSTRACT FROM PUBLISHER]

Eclosion in flies and other insects is a circadian-gated behaviour under control of a central and a peripheral clock. It is not influenced by the motivational state of an animal, and thus presents an ideal paradigm to study the relation and signalling pathways between central and peripheral clocks, and downstream peptidergic regulatory systems. Little is known, however, about eclosion rhythmicity under natural conditions, and research into this direction is hampered by the physically closed design of current eclosion monitoring systems. We describe a novel open eclosion monitoring system (WEclMon) that allows the puparia to come into direct contact with light, temperature and humidity. We demonstrate that the system can be used both in the laboratory and outdoors, and shows a performance similar to commercial closed funnel-type monitors. Data analysis is semi-automated based on a macro toolset for the open imaging software Fiji. Due to its open design, the WEclMon is also well suited for optogenetic experiments. A small screen to identify putative neuroendocrine signals mediating time from the central clock to initiate eclosion showed that optogenetic activation of ETH-, EH and myosuppressin neurons can induce precocious eclosion. Genetic ablation of myosuppressin-expressing neurons did, however, not affect eclosion rhythmicity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of digital pupillometry in the diagnosis of anisocoria related to Horner syndrome in adult patients. Design: Retrospective, observational, case control study. Methods: Nineteen patients with unilateral Horner syndrome (Horner group) and age-matched controls of 30 healthy individuals with normal vision and neither optic nerve dysfunction nor pupillary abnormalities were included. Pupillary light reflex (PLR) of the Horner group and controls were measured by a dynamic pupillometer (PLR-200; NeurOptics Inc., Irvine, USA). Minimal and maximal (min/max) pupil diameters, latency, constriction ratio, constriction velocity, dilation velocity, and total time taken by the pupil to recover 75% of maximal pupil diameter (T75) were noted. PLR were measured at baseline in both groups and at 30–45 minutes later after 0.5% apraclonidine (Iopidine®; Alcon Laboratories, Fort Worth, TX, USA) instillation in the Horner group. Main outcome measures: The PLR parameters in the affected eye and inter-eye difference before and after 0.5% apraclonidine instillation. Results: In the Horner group, pupil diameters and T75 showed significant difference between the affected eye and unaffected contralateral eye at baseline (all P<0.00625). Compared to controls, inter-eye difference values of pupil diameters and T75 were significantly larger in the Horner group (all P<0.001). After 0.5% apraclonidine instillation, changes in pupil diameter and constriction ratio were significantly larger in the affected eye compared to the unaffected contralateral eye (all P<0.00625). The area under the receiver operating characteristic curves for diagnosing Horner syndrome were largest for baseline inter-eye difference in min/max pupil sizes (AUC = 0.975, 0.994), T75 (AUC = 0.838), and change in min/max pupil sizes after apraclonidine instillation (AUC = 0.923, 0.929, respectively). The diagnostic criteria for Horner syndrome relying on baseline pupillary measurements was defined as one of the two major findings; 1) smaller maximal pupil diameter in the affected eye with an inter-eye difference of > 0.5 mm, or 2) T75 > 2.61 seconds in the affected eye, which showed a sensitivity of 94.7% and specificity of 93.3%. The diagnostic accuracy of apraclonidine testing showed a sensitivity of 84.6% and specificity of 92.3%. Conclusions: Digital pupillometry is an objective method for quantifying PLR. Baseline inter-eye difference in maximal pupil sizes and dilation lag measured by T75 was equally effective in the diagnosis of Horner syndrome compared to the reversal of anisocoria after apraclonidine instillation. [ABSTRACT FROM AUTHOR]

Information processing in neural networks depends on the connectivity among excitatory and inhibitory neurons. The presence of parallel, distinctly controlled local circuits within a cortical network may ensure an effective and dynamic regulation of microcircuit function. By applying a combination of optogenetics, electrophysiological recordings, and high resolution microscopic techniques, we uncovered the organizing principles of synaptic communication between principal neurons and basket cells in the basal nucleus of the amygdala. In this cortical structure, known to be critical for emotional memory formation, we revealed the presence of 2 parallel basket cell networks expressing either parvalbumin or cholecystokinin. While the 2 basket cell types are mutually interconnected within their own category via synapses and gap junctions, they avoid innervating each other, but form synaptic contacts with axo-axonic cells. Importantly, both basket cell types have the similar potency to control principal neuron spiking, but they receive excitatory input from principal neurons with entirely diverse features. This distinct feedback synaptic excitation enables a markedly different recruitment of the 2 basket cell types upon the activation of local principal neurons. Our data suggest fundamentally different functions for the 2 parallel basket cell networks in circuit operations in the amygdala. [ABSTRACT FROM AUTHOR]

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are important regulators of a wide range of biological processes. Antagomir studies suggest an implication of miR-132 in the functionality of the mammalian circadian clock. miR-212 and miR-132 are tandemly processed from the same transcript and share the same seed region. We found the clock modulator miR-132 and miR-212 to be expressed rhythmically in the central circadian clock. Consequently, mRNAs implicated in circadian functions may likely be targeted by both miRs. To further characterize the circadian role we generated mice with stable deletion of the miR-132/212 locus and compared the circadian behavior of mutant and wild-type control animals on two genetic backgrounds frequently used in chronobiological research, C57BL/6N and 129/Sv. Surprisingly, the wheel-running activity phenotype of miR mutant mice was highly background specific. A prolonged circadian free-running period in constant darkness was found in 129/Sv, but not in C57BL/6N miR-132/212 knockout mice. In contrast, in C57BL/6N, but not in 129/Sv miRNA-132/212 knockout mice a lengthened free-running period was observed in constant light conditions. Furthermore, miR-132/212 knockout mice on 129/Sv background exhibited enhanced photic phase shifts of locomotor activity accompanied by reduced light induction of Period gene transcription in the SCN. This phenotype was absent in miRNA-132/212 knockout mice on a C57BL/6N background. Together, our results reveal a strain and light regimen-specific function of miR-132/212 in the circadian clock machinery suggesting that miR-132 and miR-212 act as background-dependent circadian rhythm modulators. [ABSTRACT FROM AUTHOR]

The lipid-producing model alga Nannochloropsis oceanica has a distinct photosynthetic machinery. This organism possesses chlorophyll a as its only chlorophyll species, and has a high ratio of PSI to PSII. This high ratio of PSI to PSII may affect the redox state of the plastoquinone pool during exposure to light, and consequently may play a role in activating photoprotection mechanisms. We utilized pulse-amplitude modulated fluorometry to investigate the redox state of the plastoquinone pool during and after bright light pulses. Our data indicate that even very intense (5910 μmol photons s-1m-2 of blue light having a wavelength of 440 nm) light pulses of 0.8 second duration are not sufficient to completely reduce the plastoquinone pool in Nannochloropsis. In order to achieve extensive reduction of the plastoquinone pool by bright light pulses, anaerobic conditions or an inhibitor of the photosynthetic electron transport chain has to be utilized. The implication of this finding for the application of the widely used saturating pulse method in algae is discussed. [ABSTRACT FROM AUTHOR]

Objective: Analysis of the crosslink time, depth and efficacy profiles of UV-light-activated corneal collagen crosslinking (CXL). Methods: A modeling system described by a coupled dynamic equations are numerically solved and analytic formulas are derived for the crosslinking time (T*) and crosslinking depth (z*). The z-dependence of the CXL efficacy is numerically produced to show the factors characterizing the profiles. Results: Optimal crosslink depth (z*) and maximal CXL efficacy (Ceff) have opposite trend with respective to the UV light intensity and RF concentration, where z* is a decreasing function of the riboflavin concentration (C0). In comparison, Ceff is an increasing function of C0 and the UV exposure time (for a fixed UV dose), but it is a decreasing function of the UV light intensity. CXL efficacy is a nonlinear increasing function of [C0/I0]-0.5 and more accurate than that of the linear theory of Bunsen Roscoe law. Depending on the UV exposure time and depth, the optimal intensity ranges from 3 to 30 mW/cm2 for maximal CXL efficacy. For steady state (with long exposure time), low intensity always achieves high efficacy than that of high intensity, when same dose is applied on the cornea. Conclusions: The crosslinking depth (z*) and the crosslinking time (T*) have nonlinear dependence on the UV light dose and the efficacy of corneal collagen crosslinking should be characterized by both z* and the efficacy profiles. A nonlinear scaling law is needed for more accurate protocol. [ABSTRACT FROM AUTHOR]

Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be useful for early toxicity work. In pancreatic beta-cells it reveals the effects of glucose and the KATP inhibitor gliclazide. [ABSTRACT FROM AUTHOR]

The green alga Chlamydomonas reinhardtii shows various light responses in behavior and physiology. One such photoresponse is the circadian clock, which can be reset by external light signals to entrain its oscillation to daily environmental cycles. In a previous report, we suggested that a light-induced degradation of the clock protein ROC15 is a trigger to reset the circadian clock in Chlamydomonas. However, light signaling pathways of this process remained unclear. Here, we screened for mutants that show abnormal ROC15 diurnal rhythms, including the light-induced protein degradation at dawn, using a luciferase fusion reporter. In one mutant, ROC15 degradation and phase resetting of the circadian clock by light were impaired. Interestingly, the impairments were observed in response to red and violet light, but not to blue light. We revealed that an uncharacterized gene encoding a protein similar to RAS-signaling-related leucine-rich repeat (LRR) proteins is responsible for the mutant phenotypes. Our results indicate that a previously uncharacterized red/violet light signaling pathway is involved in the phase resetting of circadian clock in Chlamydomonas. [ABSTRACT FROM AUTHOR]

Martinotti cells are the most prominent distal dendrite–targeting interneurons in the cortex, but their role in controlling pyramidal cell (PC) activity is largely unknown. Here, we show that the nicotinic acetylcholine receptor α2 subunit (Chrna2) specifically marks layer 5 (L5) Martinotti cells projecting to layer 1. Furthermore, we confirm that Chrna2-expressing Martinotti cells selectively target L5 thick-tufted type A PCs but not thin-tufted type B PCs. Using optogenetic activation and inhibition, we demonstrate how Chrna2-Martinotti cells robustly reset and synchronize type A PCs via slow rhythmic burst activity and rebound excitation. Moreover, using optical feedback inhibition, in which PC spikes controlled the firing of surrounding Chrna2-Martinotti cells, we found that neighboring PC spike trains became synchronized by Martinotti cell inhibition. Together, our results show that L5 Martinotti cells participate in defined cortical circuits and can synchronize PCs in a frequency-dependent manner. These findings suggest that Martinotti cells are pivotal for coordinated PC activity, which is involved in cortical information processing and cognitive control. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy and precision of HemoCue 201 (HemoCue) and Masimo Pronto 7 (Masimo) devices for measuring hemoglobin (Hb) in epidemiological studies, having venous blood samples as a gold standard. Material and methods: We measured Hb concentrations in a field sample of 148 children from one to five years of age. Masimo and HemoCue were used for capillary blood samples and an automatic analyzer for venous blood samples. Regression models with no intercept were constructed to measure precision and predictability, concordance correlations to measure accuracy and precision, and Bland-Altman limits of agreement as well as hierarchical linear models to estimate variance. Results: Both HemoCue and Masimo underestimated Hb concentrations compared to the gold standard. They respectively yielded the following results: regression coefficients of 0.887 and 0.876 with 98.7% and 98.6% predictability; concordance correlation coefficients of 0.183 (p<0.001) and 0.166 (p<0.001); and Bland-Altman variances of -1.51 and -1.62. With regard to Masimo specifically, the three-level Hierarchical Linear Model showed that 57.9% of total variance stemmed from random errors in repeated measures from the same subject. Conclusions: HemoCue and Masimo measure lower Hb concentrations than the gold standard. Their accuracy and precision levels are comparable. It is essential to ensure proper use of devices through enhanced training of field workers. [ABSTRACT FROM AUTHOR]

Animals of the amphipodOrchestia montaguiare kept in constant darkness with two short light pulses. One pulse is applied at the beginning of subjective night (around the dusk) and the other one at the end of subjective night (around the dawn). The pulse duration is estimated in the order of one or two hours around the dusk as well as the dawn. The locomotor activity rhythm was monitored in individual animals in summer under constant temperature. Results revealed that whatever the experimental conditions, under continuous or interrupted darkness by pulses, two endogenous components have been highlighted. In fact, Periodogram analysis showed the presence of ultradian and circadian periods around 12 and 24 h, respectively. The shortest circadian period and the most important inter-individual variability was observed under pulse of 2 h around the dusk with mean value equal toτDD+pulse = 24h38′ ± 4h34′. The activity profiles are in majority unimodal. Moreover, the most activity peak showed a slipping of its location from the middle of subjective night under constant darkness to the middle of subjective day under pulse. Globally, the locomotor activity rhythm ofO. montaguiwas better defined under pulses and specimens were significantly more active under continuous darkness. Moreover, a great variability around the activity time was observed especially with pulse of 1 h. [ABSTRACT FROM PUBLISHER]

Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling—the serotonin transporter–in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior. [ABSTRACT FROM AUTHOR]

Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state. [ABSTRACT FROM AUTHOR]

We recently pointed out the important role of dermis deformation by pulsating arterial pressure in the formation of a photoplethysmographic signal at green light. The aim of this study was to explore the role of this novel finding in near-infrared (NIR) light. A light-emitting diode (LED)-based imaging photoplethysmography (IPPG) system was used to detect spatial distribution of blood pulsations under frame-to-frame switching green and NIR illumination in the palms of 34 healthy individuals. We observed a significant increase of light-intensity modulation at the heartbeat frequency for both illuminating wavelengths after a palm was contacted with a glass plate. Strong positive correlation between data measured at green and NIR light was found, suggesting that the same signal was read independently from the depth of penetration. Analysis of the data shows that an essential part of remitted NIR light is modulated in time as a result of elastic deformations of dermis caused by variable blood pressure in the arteries. Our observations suggest that in contrast with the classical model, photoplethysmographic waveform originates from the modulation of the density of capillaries caused by the variable pressure applied to the skin from large blood vessels. Particularly, beat-to-beat transmural pressure in arteries compresses/decompresses the dermis and deforms its connective-tissue components, thus affecting the distance between the capillaries, which results in the modulation of absorption and scattering coefficients of both green and NIR light. These findings are important for the correct interpretation of this widely used medical technique, which may have novel applications in diagnosis and treatment monitoring of aging and skin diseases. [ABSTRACT FROM AUTHOR]

During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles. [ABSTRACT FROM AUTHOR]

There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. [ABSTRACT FROM AUTHOR]