Kerr nonlinearity assisted magnetically induced transparency in cavity magnon polaritons.

We investigate optical transmission in cavity magnon polaritons and discover a complex multi-window magnetically induced transparency and a bistability with magnetic and optical characteristics. With the regulation of Kerr nonlinear effects and driven fields, a complex multi-window resonant transmission with fast and slow light effects appears, which includes transparency and absorption windows. The magnetically induced transparency and absorption can be explained by the destructive and constructive interference between different excitation pathways. Moreover, we demonstrate the bistability of magnons and photons with a hysteresis loop, where magnetic and optical bistabilities can induce and control each other. Our results pave a new way, to the best of our knowledge, for implementing a room-temperature multiband quantum memory.

Preparation and Evaluation of Peptides with Potential Antioxidant Activity by Microwave Assisted Enzymatic Hydrolysis of Collagen from Sea Cucumber Acaudina Molpadioides Obtained from Zhejiang Province in China.

The present study was focused on the preparation and characterization of the antioxidant peptides by microwave-assisted enzymatic hydrolysis of collagen from sea cucumber Acaudina molpadioides (ASC-Am) obtained from Zhejiang Province in China. The results exhibited the effects of microwave irradiation on hydrolysis of ASC-Am with different protease. Neutrase was selected from the four common proteases (papain, pepsin, trypsin, and neutrase) based on the highest content and DPPH scavenging activity of hydrolysate Fa (Molecular weight < 1 kDa). The content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of Fa obtained by hydrolysis of neutrase increased by 100% and 109% respectively at a microwave power of 300 W compared with no microwave irradiation. Five subfractions were obtained after performing the gel filtration chromatography, and the Fa.2 exhibited the highest DPPH scavenging activity. The amino acid analysis showed that the contents of Glutamic acid, Alanine, Tyrosine, and Phenylalanine in fraction Fa.2 increased significantly, but an obvious decrease in the content of Glycine was observed compared to Fa. Four peptides (Fa.2-A, Fa.2-B, Fa.2-C, and Fa.2-D) were purified from Fa.2 by high performance liquid chromatography, and Fa.2-C showed the highest DPPH scavenging activity. The sequence of Fa.2-C was identified as Phenylalanine-Leucine- Alanine-Proline with a half elimination ratio (EC50) of 0.385 mg/mL. The antioxidant activity of Fa.2-C was probably attributed to the small molecular sizes and the presence of hydrophobic amino acid residues in its sequence. This report provided a promising method for the preparation of antioxidant peptides from collagen for food and medicinal purposes.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits.

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of ß2 subunits of nicotinic acetylcholine receptors (ß2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that ß2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT: Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits.

Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. METHODS: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. RESULTS: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 µmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 µmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. CONCLUSION: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

Pharmacokinetic study of ofloxacin enantiomers in Pagrosomus major by chiral HPLC.

(S)-(-)-Ofloxacin and (R)-(+)-ofloxacin concentrations in the plasma of Pagrosomus major after drug treatment were detected by chiral high-performance liquid chromatography, and various pharmacokinetic parameters were calculated from these data. The elimination half-life of (S)-(-)-ofloxacin was significantly shorter than that of the (R)-(+) enantiomer. (S)-(-)-Ofloxacin also had a significantly lower maximum plasma concentration, area under the concentration-time curve from zero to infinity, and mean residence time than (R)-(+)-ofloxacin. However, the apparent volume of distribution and total body clearance of (S)-(-)-ofloxacin were greater than those of (R)-(+)-ofloxacin. The ratio of the (S)-(-)- to (R)-(+)-ofloxacin plasma concentration was always <1.0. Together, these data suggest that (S)-(-)-ofloxacin was preferentially excreted and (R)-(+)-ofloxacin was preferentially absorbed. Although the difference in pharmacokinetic parameters was small, the metabolic behavior of the ofloxacin enantiomers in P. major was enantioselective.

Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina.

Retinal light responsiveness measured via electroretinography undergoes developmental modulation, and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study was to determine whether dopamine D2 receptors regulate the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild-type mice and mice with a genetic deletion of the gene that encodes the D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that D2 receptor mutation preferentially increases the amplitude of the inner retinal light responses evoked by high-intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, i.e. a-waves, b-waves, and oscillatory potentials, increase with age. Comparatively, D2 receptor mutation preferentially reduces the age-dependent increase in b-waves evoked by low-intensity light. Light deprivation from birth reduces b-wave amplitudes and completely abolishes the increased amplitude of oscillatory potentials of D2 receptor mutants. Taken together, these results demonstrate that D2 receptors play an important role in the activity-dependent functional development of the mouse retina.

Competition driven by retinal waves promotes morphological and functional synaptic development of neurons in the superior colliculus.

Prior to eye opening, waves of spontaneous activity sweep across the developing retina. These "retinal waves," together with genetically encoded molecular mechanisms, mediate the formation of visual maps in the brain. However, the specific role of wave activity in synapse development in retino-recipient brain regions is unclear. Here we compare the functional development of synapses and the morphological development of neurons in the superior colliculus (SC) of wild-type (WT) and transgenic (ß2-TG) mice in which retinal wave propagation is spatially truncated (Xu HP, Furman M, Mineur YS, Chen H, King SL, Zenisek D, Zhou ZJ, Butts DA, Tian N, Picciotto MR, Crair MC. Neuron 70: 1115-1127, 2011). We use two recently developed brain slice preparations to examine neurons and synapses in the binocular vs. mainly monocular SC. We find that retinocollicular synaptic strength is reduced whereas the number of retinal inputs is increased in the binocular SC of ß2-TG mice compared with WT mice. In contrast, in the mainly monocular SC the number of retinal inputs is normal in ß2-TG mice, but, transiently, synapses are abnormally strong, possibly because of enhanced activity-dependent competition between local, "small" retinal wave domains. These findings demonstrate that retinal wave size plays an instructive role in the synaptic and morphological development of SC neurons, possibly through a competitive process among retinofugal axons.

Visual Deprivation Retards the Maturation of Dendritic Fields and Receptive Fields of Mouse Retinal Ganglion Cells.

It was well documented that both the size of the dendritic field and receptive field of retinal ganglion cells (RGCs) are developmentally regulated in the mammalian retina, and visual stimulation is required for the maturation of the dendritic and receptive fields of mouse RGCs. However, it is not clear whether the developmental changes of the RGC receptive field correlate with the dendritic field and whether visual stimulation regulates the maturation of the dendritic field and receptive field of RGCs in a correlated manner. The present work demonstrated that both the dendritic and receptive fields of RGCs continuously develop after eye opening. However, the correlation between the developmental changes in the receptive field size and the dendritic field varies among different RGC types. These results suggest a continuous change of synaptic converging of RGC synaptic inputs in an RGC type-dependent manner. Besides, light deprivation impairs both the development of dendritic and receptive fields.

Fabrication of Carboxymethylcellulose/Metal-Organic Framework Beads for Removal of Pb(II) from Aqueous Solution.

The ability to remove toxic heavy metals, such as Pb(II), from the environment is an important objective from both human-health and ecological perspectives. Herein, we describe the fabrication of a novel carboxymethylcellulose-coated metal organic material (MOF-5⁻CMC) adsorbent that removed lead ions from aqueous solutions. The adsorption material was characterized by Fourier-transform infrared spectroscopy, X-ray diffractometry, scanning electron microscopy, and X-ray photoelectron spectroscopy. We studied the functions of the contact time, pH, the original concentration of the Pb(II) solution, and adsorption temperature on adsorption capacity. MOF-5⁻CMC beads exhibit good adsorption performance; the maximum adsorption capacity obtained from the Langmuir isotherm-model is 322.58 mg/g, and the adsorption equilibrium was reached in 120 min at a concentration of 300 mg/L. The adsorption kinetics is well described by pseudo-second-order kinetics, and the adsorption equilibrium data are well fitted to the Langmuir isotherm model (R² = 0.988). Thermodynamics experiments indicate that the adsorption process is both spontaneous and endothermic. In addition, the adsorbent is reusable. We conclude that MOF-5⁻CMC is a good adsorbent that can be used to remove Pb(II) from aqueous solutions.

Retinal ganglion cell dendrites undergo a visual activity-dependent redistribution after eye opening.

Recent studies showed that light stimulation is required for the maturational segregation of retinal ganglion cell (RGC) synaptic connectivity with ON and OFF bipolar cells in mammalian retina. However, it is not clear to what extent light stimulation regulates the maturation of RGC dendritic ramification and synaptic connections. The present work quantitatively analyzed the dendritic ramification patterns of different morphological subtypes of RGCs of developing mouse retinas and demonstrated that RGCs in all four major morphological subtypes underwent profound dendritic redistributions from the center to specific stratum of the IPL after eye opening. Light deprivation preferentially blocked the developmental RGC dendritic redistribution from the center to sublamina a of the IPL. Interestingly, this developmental redistribution of RGC dendrites could not be explained by a simple developmental elimination of "excess" dendrites and, therefore, suggests a possible mechanism that requires both selective dendritic growth and elimination guided by visual activity.

GABAergic regulation of spontaneous spike patterns in the developing rabbit retina.

Spontaneous retinal waves play a critical role in the establishment of precise neuronal connections in the developing visual system. Retinal waves in mammals progress through three distinct developmental stages prior to eye opening. Using multielectrode array (MEA) recording from the rabbit retina, this study found characteristic changes in the spontaneous spike pattern in the ganglion cell layer during the transition from stage II to stage III retinal waves. These changes led to an increased diversity in the spatiotemporal pattern of the spontaneous activity, consistent with a potential role of stage III retinal waves in the establishment of diverse, cell type-specific neuronal connectivity during visual system development. The study also showed that GABAergic inhibition, predominantly mediated by GABAA receptors, was critical in breaking down large waves of ganglion cell spiking into spatially restricted and temporally diverse spike patterns at stage III, suggesting an important role of amacrine cells in shaping the diverse spontaneous activity patterns of developing ganglion cells.

Spatial pattern of spontaneous retinal waves instructs retinotopic map refinement more than activity frequency.

Spontaneous activity during early development is necessary for the formation of precise neural connections, but it remains uncertain whether activity plays an instructive or permissive role in brain wiring. In the visual system, retinal ganglion cell (RGC) projections to the brain form two prominent sensory maps, one reflecting eye of origin and the other retinotopic location. Recent studies provide compelling evidence supporting an instructive role for spontaneous retinal activity in the development of eye-specific projections, but evidence for a similarly instructive role in the development of retinotopy is more equivocal. Here, we report on experiments in which we knocked down the expression of ß2-containing nicotinic acetylcholine receptors (ß2-nAChRs) specifically in the retina through a Cre-loxP recombination strategy. Overall levels of spontaneous retinal activity in retina-specific ß2-nAChR mutant mice (Rx-ß2cKO), examined in vitro and in vivo, were reduced to a degree comparable to that observed in whole animal ß2-nAChR mouse mutants (ß2KO). However, many residual spontaneous waves in Rx-ß2cKO mice displayed local propagating features with strong correlations between nearby but not distant RGCs typical of waves observed in wild-type (WT) but not ß2KO mice. We further observed that eye-specific segregation was disrupted in Rx-ß2cKO mice, but retinotopy was spared in a competition-dependent manner. These results suggest that propagating patterns of spontaneous retinal waves are essential for normal development of the retinotopic map, even while overall activity levels are significantly reduced, and support an instructive role for spontaneous retinal activity in both eye-specific segregation and retinotopic refinement.

Different effects of low Ca2+ on signal transmission from rods and cones to bipolar cells in carp retina.

Modulation of signal transmission from rods, red-sensitive (R-) and green-sensitive (G-) cones to bipolar cells by lowering extracellular Ca(2+) was studied in the isolated superfused carp retina using intracellular recording techniques. Low Ca(2+) (nominally Ca(2+)-free) potentiated light responses of rod dominant ON bipolar cells (rod-ON-BCs). On the other hand, responses of cone dominant ON bipolar cells (cone-ON-BCs) driven by G-cones were dramatically decreased whereas those driven by R-cones were hardly changed in low Ca(2+). Similar effects were observed in scotopic and photopic electroretinographic (ERG) b waves, which reflect the activities of ON-BCs driven by rods and cones, respectively. IBMX (100 microM), an inhibitor of PDE, whose effects mimic those of low Ca(2+) on phototransduction, increased responses of both rod-ON-BCs and cone-ON-BCs, suggesting that the distinct effects of low Ca(2+) described above are attributable to differential modulation of signal transfer from different types of photoreceptors to BCs. Moreover, scotopic ERG P III responses, reflecting the rod activity, were potentiated both in low Ca(2+) and in the presence of IBMX (100 microM). Low Ca(2+) causes multiple changes in the outer retina, including increase of glutamate release from the photoreceptor terminal, increase of current and voltage responses of photoreceptors to light, alteration of the synaptic gain from photoreceptors to BCs and modulation of mGluR6 pathway in the rod-ON-BCs. Interplay of these changes may account for differential modulation of R-cone and G-cone driven BC responses, as well as the different effects on rod- and cone-ON-BCs.

Expression of voltage-dependent calcium channel subunits in the rat retina.

The expression patterns of different Ca(2+) channel alpha(1) subunits (alpha(1A-E)) were immunohistochemically studied in the rat retina. Intense immunoreactivity (IR) for alpha(1A) (P/Q-type) and alpha(1B) (N-type) Ca(2+) channels was observed in both the outer and inner plexiform layers (OPL and IPL). In addition, alpha(1B)-IR was found in the outer and inner nuclear layers. Staining for alpha(1E) (R-type) was diffusely distributed in all three nuclear layers and in the IPL. The alpha(1C) and alpha(1D), two L-type Ca(2+) channel subunits, exhibited distinct expression patterns, with alpha(1C) being almost exclusively expressed on bipolar cells, and alpha(1D) mainly on photoreceptor cell bodies and in the OPL. Staining for alpha(1D) was also observed on Müller cells. The differential expression pattern of the alpha(1) subunits suggests that these Ca(2+) channel subtypes may be associated with different retinal functions.

A general principle governs vision-dependent dendritic patterning of retinal ganglion cells.

Dendritic arbors of retinal ganglion cells (RGCs) collect information over a certain area of the visual scene. The coverage territory and the arbor density of dendrites determine what fraction of the visual field is sampled by a single cell and at what resolution. However, it is not clear whether visual stimulation is required for the establishment of branching patterns of RGCs, and whether a general principle directs the dendritic patterning of diverse RGCs. By analyzing the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs underwent a substantial spatial rearrangement after eye-opening. Light deprivation blocked both the dendritic growth and the branch patterning, suggesting that visual stimulation is required for the acquisition of specific branching patterns of RGCs. We further showed that vision-dependent dendritic growth and arbor refinement occurred mainly in the middle portion of the dendritic tree. This nonproportional growth and selective refinement suggest that the late-stage dendritic development of RGCs is not a passive stretching with the growth of eyes, but rather an active process of selective growth/elimination of dendritic arbors of RGCs driven by visual activity. Finally, our data showed that there was a power law relationship between the coverage territory and dendritic arbor density of RGCs on a cell-by-cell basis. RGCs were systematically less dense when they cover larger territories regardless of their cell type, retinal location, or developmental stage. These results suggest that a general structural design principle directs the vision-dependent patterning of RGC dendrites.

Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors.

The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.

Dopamine D1 receptors regulate the light dependent development of retinal synaptic responses.

Retinal synaptic connections and function are developmentally regulated. Retinal synaptic activity plays critical roles in the development of retinal synaptic circuitry. Dopamine receptors have been thought to play important roles in the activity-dependent synaptic plasticity in central nervous system. The primary goal of this study is to determine whether dopamine D1 receptor regulates the activity-dependent development of retinal light responsiveness. Accordingly, we recorded electroretinogram from wild type mice and mice with genetic deletion of D1 dopamine receptor (D1-/- mice) raised under cyclic light conditions and constant darkness. Our results demonstrated that D1-/- mice have reduced amplitudes of all three major components of electroretinogram in adulthood. When the relative strength of the responses is considered, the D1-/- mice have selective reduction of the amplitudes of a-wave and oscillatory potentials evoked by low-intermediate intensities of lights. During postnatal development, D1-/- mice have increased amplitude of b-wave at the time of eye-opening but reduced developmental increase of the amplitude of b-wave after eye opening. Light deprivation from birth significantly reduced the amplitudes of b-wave and oscillatory potentials, increased the outer retinal light response gain and altered the light response kinetics of both a- and b-waves of wild type mice. In D1-/- mice, the effect of dark rearing on the amplitude of oscillatory potentials was diminished and dark rearing induced effects on the response gain of outer retina and the kinetics of a-wave were reversed. These results demonstrated roles of dopamine D1 receptor in the activity-dependent functional development of mouse retina.

Role of adenylate cyclase 1 in retinofugal map development.

The development of topographic maps of the sensory periphery is sensitive to the disruption of adenylate cyclase 1 (AC1) signaling. AC1 catalyzes the production of cAMP in a Ca2+/calmodulin-dependent manner, and AC1 mutant mice (AC1−/−) have disordered visual and somatotopic maps. However, the broad expression of AC1 in the brain and the promiscuous nature of cAMP signaling have frustrated attempts to determine the underlying mechanism of AC1-dependent map development. In the mammalian visual system, the initial coarse targeting of retinal ganglion cell (RGC) projections to the superior colliculus (SC) and lateral geniculate nucleus (LGN) is guided by molecular cues, and the subsequent refinement of these crude projections occurs via an activity-dependent process that depends on spontaneous retinal waves. Here, we show that AC1−/− mice have normal retinal waves but disrupted map refinement. We demonstrate that AC1 is required for the emergence of dense and focused termination zones and elimination of inaccurately targeted collaterals at the level of individual retinofugal arbors. Conditional deletion of AC1 in the retina recapitulates map defects, indicating that the locus of map disruptions in the SC and dorsal LGN of AC1−/− mice is presynaptic. Finally, map defects in mice without AC1 and disrupted retinal waves (AC1−/−;ß2−/− double KO mice) are no worse than those in mice lacking only ß2−/−, but loss of AC1 occludes map recovery in ß2−/− mice during the second postnatal week. These results suggest that AC1 in RGC axons mediates the development of retinotopy and eye-specific segregation in the SC and dorsal LGN.

Visual map development depends on the temporal pattern of binocular activity in mice.

Binocular competition is thought to drive eye-specific segregation in the developing visual system, potentially through Hebbian synaptic learning rules that are sensitive to correlations in afferent activity. Altering retinal activity can disrupt eye-specific segregation, but little is known about the temporal features of binocular activity that modulate visual map development. We used optogenetic techniques to directly manipulate retinal activity in vivo and identified a critical period before eye opening in mice when specific binocular features of retinal activity drive visual map development. Synchronous activation of both eyes disrupted segregation, whereas asynchronous stimulation enhanced segregation. The optogenetic stimulus applied was spatially homogenous; accordingly, retinotopy of ipsilateral projections was markedly perturbed, but contralateral retinotopy was unaffected or even improved. These results provide direct evidence that the synchrony and precise temporal pattern of binocular retinal activity during a critical period in development regulates eye-specific segregation and retinotopy in the developing visual system.

An instructive role for patterned spontaneous retinal activity in mouse visual map development.

Complex neural circuits in the mammalian brain develop through a combination of genetic instruction and activity-dependent refinement. The relative role of these factors and the form of neuronal activity responsible for circuit development is a matter of significant debate. In the mammalian visual system, retinal ganglion cell projections to the brain are mapped with respect to retinotopic location and eye of origin. We manipulated the pattern of spontaneous retinal waves present during development without changing overall activity levels through the transgenic expression of ß2-nicotinic acetylcholine receptors in retinal ganglion cells of mice. We used this manipulation to demonstrate that spontaneous retinal activity is not just permissive, but instructive in the emergence of eye-specific segregation and retinotopic refinement in the mouse visual system. This suggests that specific patterns of spontaneous activity throughout the developing brain are essential in the emergence of specific and distinct patterns of neuronal connectivity.