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.

Molecular characteristics of gastric cancer with ERBB2 amplification.

Gastric cancer is a prevalent malignancy with a high degree of heterogeneity, which has led to a poor therapeutic response. Though there are numerous HER2-targeted medicines for HER2+ gastric cancer, many trials have not indicated an improvement in overall survival. Here 29 ERBB2 amplification (ERBB2-Amp) type gastric cancer samples with WES and RNA-seq data were selected for investigation, which copy-number aberration (CNA) was +2. Initially, the somatic mutation and copy number variant (CNV) of them, which might cause resistance to HER2-targeted therapies, were systematically investigated evaluated, as well as their mutation signatures. Moreover, 37 modules were identified using weighted gene co-expression network analysis (WGCNA), including the blue module related to DFS status and lightcyan module correlated with ARHGAP26_ARHGAP6_CLDN18 rearrangement. In addition, focal adhesion and ECM-receptor interaction pathways were considerably enriched in the turquoise module with ERBB2 gene. ExportNetworkToCytoscape determined that MIEN1 and GRB7 are tightly connected to ERBB2., Finally, 14 single-cell intestinal gastric cancer samples were investigated, and it was shown that the TFAP2A transcription factor regulon was highly expressed in ERBB2high group, as was the EMT score. Overall, our data provide comprehensive molecular characteristics of ERBB2-Amp type gastric cancer, which offers additional information to improve HER2-targeted gastric cancer treatment.

Changes of Melanopsin Expression in the Retina of Guinea Pig during Experimental Myopia and Recovery Period.

PURPOSE: To explore whether melanopsin is associated with the development of myopia. METHODS: Seventy-two guinea pigs (3 weeks older) were randomly assigned to 6 groups: the form-deprivation myopia (FDM) group (monocularly covering the right eye for 14 days, n = 15), the FDM recovery group (removing the eye mask for 3 days, n = 13), the lens-induced myopia (LIM) group (monocularly wearing a -4D lens for 3 days, n = 15), the LIM recovery group (removing the lens for 2 days, n = 13), and another 2 age-matched normal groups (n = 8 each). The diopter, the vitreous chamber depth (VCD), and the axial length (AXL) were measured to confirm the effect of the treatments. Immunofluorescence and western blotting methods were used to examine the expression of melanopsin in the retina. RESULTS: Immunofluorescent results showed that in the FDM group, the melanopsin intensity in the retina of experimental eyes significantly decreased compared to those of contralateral eyes, but no significant difference was observed during their recovery periods. Western blotting showed that the expression of melanopsin in the experimental eyes of the FDM group was lower than that of the contralateral eyes (fold: 1.00 versus 1.36). The expression of melanopsin in the experimental eyes increased 3 days after removing form deprivation, although a slight reduction in melanopsin expression compared to that of the contralateral eyes (fold: 1.41 versus 1.58). For the LIM group, immunofluorescent showed an obvious decreased intensity of melanopsin-labeled cells in the experimental eyes compared to the contralateral eyes. Western blotting showed that although melanopsin expression in the experimental eyes decreased compared to that of the contralateral eyes (fold: 1.00 versus 1.96), no differences were found between two eyes 2 days after lens removal (fold: 1.99 versus 2.00). CONCLUSION: The decreased expression of melanopsin in the retina may potentially participate in the development of FDM and LIM.

In vitro Antitumor Properties of Fucoidan-Coated, Doxorubicin-Loaded, Mesoporous Polydopamine Nanoparticles.

Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.

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.

Affinity-binding immobilization of D-amino acid oxidase on mesoporous silica by a silica-specific peptide.

Enzyme immobilization is widely used for large-scale industrial applications. However, the weak absorption through physical methods limits the recovery ability. Here, affinity-binding immobilization of enzymes was explored using a silica-specific affinity peptide (SAP) as a fusion tag to intensify the binding force between the enzyme and mesoporous silica (MPS) carrier. D-amino acid oxidase (DAAO) of Rhodosporidium toruloides was used as a model enzyme. The optimal screened SAP (LPHWHPHSHLQP) was selected from a M13 phage display peptide library and fused to the C-terminal of DAAO to obtain fused DAAOs with one, two and three SAP tags, respectively. The activity of DAAO-SAP-MPS was superior comparing with DAAO-2SAP-MPS and DAAO-3SAP-MPS; meanwhile DAAO-SAP-MPS shows 36% higher activity than that of DAAO-MPS. Fusion with one SAP improved the thermal stability with a 10% activity increase for immobilized DAAO-SAP-MPS compared to that of DAAO-MPS at 50 °C for 3 h. Moreover, the activity recovery of immobilized DAAO-SAP-MPS was 25% higher in operation stability assessment after six-batch conversions of cephalosporin to glutaryl-7-amino cephalosporanic acid than that of DAAO-MPS.

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.

Adsorption of diclofenac sodium on bilayer amino-functionalized cellulose nanocrystals/chitosan composite.

Residual diclofenac sodium (DS) in the environment is harmful to human health. A promising method for DS removal is the use of adsorbents functionalized with amino groups that can form an ionic bond with the carboxyl group of DS at a suitable pH. In this work, a novel composite adsorbent composed of cellulose nanocrystals (CNC) and chitosan (CS) has been synthesized and functionalized by ethylenediamine (ED) in both layers. Characterization methods, including scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectrometry, and X-ray photoelectron spectroscopy, were used to confirm the morphology and synthetic mechanism of the double- amino-functionalized adsorbent. Based on the optimization of adsorption conditions and modeling of the adsorption mechanism, the DS adsorption process on CNC-ED@CS-ED involves chemical adsorption, and the maximum adsorption capacity obtained from the Langmuir model is 444.44 mg/g. CNC-ED@CS-ED exhibits good adsorption capacity and high sustainability; thus, it is a promising composite material for the removal of DS from wastewater.

OFS plus AI or SERM vs. SERM alone in premenopausal women with hormone receptor-positive breast cancer: a prospective cohort study using the real-world database.

BACKGROUND: Ovarian function suppression (OFS) plus other endocrine treatment was recommended to hormone receptor (HR)-positive breast cancer by some guidelines recently. We performed this study to validate the survival benefits of OFS plus aromatase inhibitors (AI) or selective estrogen receptor modulators (SERM) in the real world. METHODS: All premenopausal, HR-positive breast cancer patients diagnosed between 1996 and 2017 were identified. Eligible patients were classified into three groups according to their adjuvant endocrine treatment, including OFS plus AI, OFS plus SERM and SERM alone. The primary outcome is invasive disease-free survival (iDFS), whereas the secondary outcome is overall survival (OS). Cox proportional hazards models and propensity score adjusted models were used to compare the survival benefits in three groups. RESULTS: We included 2838 patients, of which 246 received OFS plus AI, 175 received OFS plus SERM, and 2417 received SERM alone. Compared with SERM alone, OFS plus AI was associated with an improved iDFS (HR 0.59, 95% CI 0.36-0.96) and OS (HR 0.26, 95% CI 0.08-0.85). OFS plus SERM, however, was not significantly associated with extended iDFS or OS. Among patients older than 40 years old, OFS plus AI was more effective than OFS plus SERM (HR 0.38, 95% CI 0.17-0.88) or SERM alone (HR 0.44, 95% CI 0.23-0.84) in terms of iDFS. CONCLUSIONS: Our findings suggest that OFS plus AI treatment may extend both iDFS and OS among premenopausal patients with hormone receptor-positive breast cancer in the real world.

A novel benzothiazole-based fluorescent probe for cysteine detection and its application on test paper and in living cells.

A novel simple and readily synthesized turn-on fluorescent probe 4-(benzo[d]thiazol-2-yl)-1,3-phenylene bis(2-chloroacetate) (BPBC) for cysteine (Cys) was reported. This probe was designed based on an excited-state intramolecular proton transfer (ESIPT) dye: benzothiazole, and two chloroacetate groups present in benzothiazole as the reaction sites for Cys. It shows high selectivity and sensitivity for Cys over other amino acids including the similar structured homocysteine (Hcy) and glutathione (GSH). In addition, probe BPBC was successfully applied to bioimage intracellular Cys in living cells with low cytotoxicity. More importantly, a paper test strip system was developed with probe BPBC for Cys detection conveniently.

Inhibitory effect of caveolin-1 in vascular endothelial cells, pericytes and smooth muscle cells.

Caveolin-1 (Cav1) is the principle structural protein of caveolae. It plays important roles in the vascular system under both physiological and pathological conditions. Although Cav1 has been shown to inhibit microvascular permeability and has been considered as a tumor-suppressor for years, the underlying cellular mechanism has yet to be discovered. Here, we systematically investigated Cav1 functions in the main types of vascular cells, including endothelial cells (ECs), pericytes (PCs) and smooth muscle cells (SMCs). We synthesized a cell-permeable peptide called cavtratin that is derived from the Cav1 scaffolding domain. We found that cavtratin inhibited ECs in all assays, including survival, proliferation, migration and permeability assays. It also inhibited the proliferation of PCs and SMCs but had no effect on their survival or migration. The inhibitory effect of cavtratin on the proliferation of all vascular cells suggests that Cav1 plays important roles in vascular development and angiogenesis. Under physiological condition, the main function of Cav1 is to inhibit EC permeability.

Caveolin-1 Protects Retinal Ganglion Cells against Acute Ocular Hypertension Injury via Modulating Microglial Phenotypes and Distribution and Activating AKT pathway.

Glaucoma, a group of eye diseases, causes gradual loss of retinal ganglion cells (RGCs) and ultimately results in irreversible blindness. Studies of the underlying mechanisms of glaucoma and clinical trial are far from satisfactory. Results from a genome-wide association study have suggested that the CAV1/CAV2 locus is associated with glaucoma, but this association and its potential underlying mechanisms need to be confirmed and further explored. Here, we studied the function of caveolin-1 (Cav1) in an acute ocular hypertension glaucoma model. Cav1 deficiency caused an aggregated lesion in the retina. In addition, treatment with cavtratin, a membrane permeable Cav1 scaffolding domain peptide, enhanced RGC survival. After cavtratin treatment, microglial numbers decreased significantly, and the majority of them migrated from the inner retinal layer to the outer retinal layers. Furthermore, cavtratin promoted a change in the microglia phenotype from the neurotoxic pro-inflammatory M1 to the neuroprotective anti-inflammatory M2. In a molecular mechanism experiment, we found that cavtratin activated the phosphorylation of both AKT and PTEN in cultured N9 cells. Our data highlights the neuroprotective effect of Cav1 on acute ocular hypertension and suggests that Cav1 may serve as a novel therapeutic target for the treatment of glaucoma. We further propose that cavtratin is a therapeutic candidate for glaucoma clinical trials.

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.

Novel Waterborne UV-Curable Hyperbranched Polyurethane Acrylate/Silica with Good Printability and Rheological Properties Applicable to Flexographic Ink.

Novel waterborne UV-curable hyperbranched polyurethane acrylate/silica (HBWPUA/SiO2) nanocomposites were prepared by a three-step procedure and sol-gel method. 1H NMR and 13C NMR results indicate that HBWPU is successfully synthesized. Surface tension and contact angle tests both demonstrate the good wettability of the nanocomposites. Besides, the kinetics of photopolymerization of HBWPUA/SiO2 films were analyzed by attenuated total reflection-Fourier transform infrared spectroscopy, which reveals that the modified SiO2 could accelerate the curing speed of HBWPUA coatings. Thermal gravity analysis indicates that the HBWPUA/SiO2 hybrid films have a better thermal stability than the pure HBWPUA cured films. Furthermore, the hybrid films show enhanced pencil hardness, abrasion resistance, and adhesion. On the basis of the above, HBWPUA/SiO2 nanocomposites were finally applied to waterborne UV-curing flexographic printing ink, which is printed on poly(ethylene terephthalate) and glass. The nanocomposite presents good rheological behavior because the ink has a lower Z 0, a higher Z ∞, and the viscosity rebuild time is 375 s. Three colors (red, yellow, and blue) of ink were used to test its printing quality, the curing time was below 30 s, and the adhesion was excellent without being stripped. All of the inks show good water resistance and abrasion resistance. Moreover, the red and blue inks possess better solid densities than the value of 1.07 of yellow ink, and are 1.83 and 1.84, respectively. The current study suggests that the process has promise in applications of food packages.

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.

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.

A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa.

Retinitis pigmentosa is a leading cause of inherited blindness, with no effective treatment currently available. Mutations primarily in genes expressed in rod photoreceptors lead to early rod death, followed by a slower phase of cone photoreceptor death. Rd1 mice provide an invaluable animal model to evaluate therapies for the disease. We previously reported that overexpression of histone deacetylase 4 (HDAC4) prolongs rod survival in rd1 mice. Here we report a key role of a short N-terminal domain of HDAC4 in photoreceptor protection. Expression of this domain suppresses multiple cell death pathways in photoreceptor degeneration, and preserves even more rd1 rods than the full-length HDAC4 protein. Expression of a short N-terminal domain of HDAC4 as a transgene in mice carrying the rd1 mutation also prolongs the survival of cone photoreceptors, and partially restores visual function. Our results may facilitate the design of a small protein therapy for some forms of retinitis pigmentosa.

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.