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Wnt signaling induces neurite outgrowth in mouse retinal ganglion cells
摘要： Wingless-type (Wnt) signaling pathways mediate axonal growth and remodeling in the embryonic optic nerve, brain and spinal cord. Recent studies demonstrated that the canonical Wnt/β-catenin signaling pathway also induces axonal regeneration after injury in the optic nerve of adult animals. However, the molecular mechanisms of Wnt-mediated axonal growth are not well understood. Additionally, because Wnt signaling is stimulated in neurons as well as neighboring non-neuronal cells, the cell type(s) responsible for Wnt-induced axonal regeneration are not known. The objectives of this study were to investigate potential mechanisms and target cells of Wnt3a stimulated neurite growth using primary retinal ganglion cell (RGC) cultures. We demonstrated that Wnt3a ligand induced dose-dependent increases in average neurite length and number of neurites in RGCs. QPCR analysis of candidate mediators showed that Wnt3a-dependent neurite growth was associated with lower expression of Ripk1 and Ripk3 genes. Additionally, inhibiting Ripk1 signaling with Necrostatin-1s led to increased neurite number per cell but not increased neurite length. Therefore, Ripk signaling may be involved in mediating the effects of Wnt3a on neurite number but Ripk activity does not seem to be required for Wnt3a-dependent regulation of neurite length. This study shows that RGCs are direct cellular targets of Wnt3a-induced axonal growth, and we identified a novel association between Wnt signaling and Rip kinases in neurite formation.
关键词： retina,Ripk1,axon,retinal ganglion cell,neurite growth,Wnt signaling
更新于2025-11-21 11:24:58
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Optogenetic stimulation of Gs-signaling in the heart with high spatio-temporal precision
摘要： The standard technique for investigating adrenergic effects on heart function is perfusion with pharmaceutical agonists, which does not provide high temporal or spatial precision. Herein we demonstrate that the light sensitive Gs-protein coupled receptor JellyOp enables optogenetic stimulation of Gs-signaling in cardiomyocytes and the whole heart. Illumination of transgenic embryonic stem cell-derived cardiomyocytes or of the right atrium of mice expressing JellyOp elevates cAMP levels and instantaneously accelerates spontaneous beating rates similar to pharmacological β-adrenergic stimulation. Light application to the dorsal left atrium instead leads to supraventricular extrabeats, indicating adverse effects of localized Gs-signaling. In isolated ventricular cardiomyocytes from JellyOp mice, we find increased Ca2+ currents, fractional cell shortening and relaxation rates after illumination enabling the analysis of differential Gs-signaling with high temporal precision. Thus, JellyOp expression allows localized and time-restricted Gs stimulation and will provide mechanistic insights into different effects of site-specific, long-lasting and pulsatile Gs activation.
关键词： β-adrenergic stimulation,Optogenetic stimulation,spatio-temporal precision,JellyOp,Gs-signaling,cAMP,cardiomyocytes,heart
更新于2025-11-21 11:24:58
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[IEEE 2018 IEEE International Conference on Computer and Communication Engineering Technology (CCET) - Beijing, China (2018.8.18-2018.8.20)] 2018 IEEE International Conference on Computer and Communication Engineering Technology (CCET) - Lightweight Security Signaling Mechanism in Optical Network for Smart Power Grid
摘要： The communication security issue brought by Smart Grid is of great importance and should not be ignored in backbone optical networks. With the aim to solve this problem, this paper firstly conducts deep analysis into the security challenge of optical network under smart power grid environment and proposes a so-called lightweight security signaling mechanism of multi-domain optical network for Energy Internet. The proposed scheme makes full advantage of current signaling protocol with some necessary extensions and security improvement. Thus, this lightweight security signaling protocol is designed to make sure the end-to-end trusted connection. Under the multi-domain communication services of smart power grid, evaluation simulation for the signaling interaction is conducted. Simulation results show that this proposed approach can greatly improve the security level of large-scale multi-domain optical network for smart power grid with better performance in term of connection success rate performance.
关键词： Smart grid,security signaling,signaling encryption,multi-domain optical network,trusted connection
更新于2025-09-23 15:22:29
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Expression and significance of the Hedgehog signal transduction pathway in oxygen-induced retinal neovascularization in mice
摘要： Aim: The aim of the study was to investigate the signal transduction mechanism of Hedgehog–vascular endothelial growth factor in oxygen-induced retinopathy (OIR) and the effects of cyclopamine on OIR. Methods: An OIR model was established in C57BL/6J mice exposed to hyperoxia. Two hundred mice were randomly divided into a control group, an OIR group, an OIR-control group (treated with isometric phosphate-buffered saline by intravitreal injection), and a cyclopamine group (treated with cyclopamine by intravitreal injection), with 50 mice in each group. The retinal vascular morphology was observed using adenosine diphosphatase and number counting using hematoxylin and eosin-stained image. Quantitative real-time quantitative polymerase chain reaction was used to detect mRNA expression. Protein location and expression were evaluated using immunohistochemistry and Western blot. Results: The OIR group and OIR-control group demonstrated large-area pathological neovascularization and nonperfused area when compared with the control group (both P<0.05). The area of nonperfusion and neovascularization in the cyclopamine group was significantly reduced compared with the OIR and OIR-control groups (both P<0.05). Compared with the control group, the OIR and OIR-control groups had more vascular endothelial cells breaking through the inner limiting membrane. The number of new blood vessel endothelial cell nuclei in the cyclopamine group was significantly reduced (both P<0.05) when compared with the OIR and OIR-control groups. The mRNA and protein expressions of Smoothened, Gli1, and vascular endothelial growth factor in the signal pathway of the OIR and OIR-control groups were significantly higher than those of the control group; however, in the cyclopamine group, these factors were reduced when compared with the OIR and OIR-control groups (all P<0.05). Conclusion: Our data suggest that abnormal expression of the Hedgehog signaling pathway may be closely associated with the formation of OIR. Inhibiting the Smoothened receptor using cyclopamine could control retinal neovascularization, providing new ideas and measures for the prevention of oxygen-induced retinal neovascularization.
关键词： neovascularization,retinopathy of prematurity,oxygen-induced retinopathy,Hedgehog signaling pathway,cyclopamine
更新于2025-09-23 15:22:29
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A Performance Comparison of Centralized and Distributed Spectrum Management Techniques in Elastic Optical Networks
摘要： Elastic optical networks (EONs) have emerged to provide higher spectrum efficiency than traditional Dense Wavelength-Division-Multiplexing (DWDM) by utilizing enabling technologies such as flexible spectrum grid, Orthogonal Frequency Division Multiplexing (OFDM), and distance adaptive rate and modulation. The choice of the control-plane is an important consideration when deploying any new technology, especially in optical networks. This paper considers generic distributed and centralized spectrum assignment policies in conjunction with the accompanying connection set-up signaling protocols in EONs. A network simulator for Generalized Multiprotocol Label Switching (GMPLS) was developed with Forward Reservation Protocol and Backward Reservation Protocol signaling methods. These signaling techniques are used with the First Fit (FF) and Random Fit (RF) Routing and Spectrum Allocation (RSA) algorithms. The paper discusses control elements (central and distributed architectures) decisions under busy hour and normal network conditions and presents a comprehensive performance analysis of key performance metrics such as connection success rate, connection establishment time, and capacity requirement.
关键词： distributed control,signaling protocols,GMPLS,routing and spectrum allocation,centralized control,spectrum allocation,Elastic optical networks
更新于2025-09-23 15:22:29
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Direct Regulation of Phytohormone Actions by Photoreceptors
摘要： Plants must adjust their growth and development adaptively in response to light. Four recent studies have now established novel paradigms connecting light and hormone signaling pathways, in which photoreceptors adopt three modes to directly regulate internal hormonal responses to external stimuli. Being sessile organisms, plants are equipped with the capacity to sense environmental information and adjust their growth and development accordingly. Light is one of the most important environmental factors, and exposure to light widely and profoundly regulates plant developmental processes (known as photomorphogenesis). To precisely sense the light signal, plants employ a series of photoreceptors across the spectrum of light. The red/far-red light (600–750 nm) receptors are members of phytochrome family, which contains five members (phyA to phyE) in arabidopsis (Arabidopsis thaliana). Cryptochromes, phototropins, and the ZEITLUPE family members sense the blue light (350–500 nm). UVR8 (UV RESISTANCE LOCUS 8) is the UV-B light (275–320 nm) receptor for UV-B responses. Plants track the status of their light environment, transduce the signals to the nucleus, and ultimately direct gene expression changes to induce light responses. Without developing a nervous system, plants have evolved phytohormones which act as internal chemical messengers for multicellular communication and coordinating plant growth and development in adaptation to various environmental conditions.
关键词： phytohormones,photomorphogenesis,photoreceptors,hormone signaling,light signaling
更新于2025-09-23 15:21:21
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Raman Spectroscopic Analysis of Signaling Molecules–Dopamine Receptors Interactions in Living Cells
摘要： The selective interaction of signaling compounds including neurotransmitters and drugs with the dopamine receptors (DARs) is extremely important for the treatment of neurodegenerative diseases. Here, we report a method to probe the selective interactions of signaling compounds with D1 and D2 DARs in living cells using the combined approach of theoretical calculation and surface-enhanced Raman spectroscopy (SERS). When signaling compounds such as DA, amphetamine, methamphetamine, and methylenedioxypyrovalerone interact with D1 dopamine receptors (DRD1), the intracellular cyclic adenosine monophosphate (cAMP) level is increased. However, the intracellular level of cAMP is decreased when D2 dopamine receptors (DRD2) interact with the abovementioned signaling compounds. In our experiments, we have internalized the silica-coated silver nanoparticles (AgNP@SiO2) in living cells to adsorb biologically generated cAMP which was probed by using SERS. Besides adsorptions of cAMP, AgNP@SiO2 has a crucial role for the enhancement of Raman cross section of the samples. We observed the characteristic SERS peaks of cAMP when DRD1-overexpressed cells interact with the signaling compounds; these peaks were not observed for other cells including DRD2-overexpressed and DRD1?DRD2-coexpressed cells. Our experimental approach is successful to probe the intracellular cAMP and characterize the selectivity of signaling compounds to different types of DARs. Furthermore, our experimental approach is highly capable for in vivo studies because it can probe intracellular cAMP using a low input power of incident laser without significant cell damage. Our experimental results and density functional theory calculations showed that 780 and 1503 cm?1 are signature Raman peaks of cAMP. The SERS peak at 780 cm?1 is associated with C?O, C?C, and C?N stretching and symmetric and asymmetric bending of two O?H bonds of cAMP, whereas the SERS peak at 1503 cm?1 is contributed by the O9?H3 bending mode.
关键词： cyclic adenosine monophosphate,living cells,signaling compounds,dopamine receptors,surface-enhanced Raman spectroscopy
更新于2025-09-23 15:21:21
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New Derivatization Reagent for Detection of free Thiol-groups in Metabolites and Proteins in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
摘要： Several diseases are associated with disturbed redox signaling and altered metabolism of sulfur-containing metabolites and proteins. Importantly, oxidative degradation of fresh-frozen tissues begins within the normal timescale of MALDI MSI sample preparation. As a result, analytical methods that preserve the redox state of the tissue are urgently needed for refined studies of the underlying mechanisms. Nevertheless, no derivatization strategy for free sulfhydryl groups in tissue is known for MALDI MSI. Here, we report the first derivatization reagent, (E)-2-cyano-N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-3-(4-hydroxyphenyl)acrylamide (CHC-Mal), for selective detection of free thiols using MALDI MSI. We performed in-situ derivatization of free thiol groups from thiol-containing metabolites such as glutathione and cysteine and reduced proteins such as insulin and imaged their spatial distribution in porcine and mouse xenograft tissue. Derivatization of thiol-containing metabolites with CHC-Mal for MALDI MSI was also possible when using aged tissue in the presence of excess reducing agents. Importantly, CHC-Mal-derivatized low mass-metabolites could be detected without the use of a conventional MALDI matrix.
关键词： redox signaling,sulfur-containing metabolites,MALDI MSI,derivatization reagent,free thiol-groups
更新于2025-09-23 15:21:01
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Unimolecular FRET sensors: Simple linker designs and properties
摘要： Protein activation and deactivation is central to a variety of biological mechanisms, including cellular signaling and transport. Unimolecular fluorescent resonance energy transfer (FRET) probes are a class of fusion protein sensors that allow biologists to visualize using an optical microscope whether specific proteins are activated due to the presence nearby of small drug-like signaling molecules, ligands or analytes. Often such probes comprise a donor fluorescent protein attached to a ligand binding domain, a sensor or reporter domain attached to the acceptor fluorescent protein, with these ligand binding and sensor domains connected by a protein linker. Various choices of linker type are possible ranging from highly flexible proteins to hinge-like proteins. It is also possible to select donor and acceptor pairs according to their corresponding F¨oster radius, or even to mutate binding and sensor domains so as to change their binding energy in the activated or inactivated states. The focus of the present work is the exploration through simulation of the impact of such choices on sensor performance.
关键词： FRET Microscopy,Fusion Proteins,Diagnostics,Monte Carlo Simulation,Coarse Graining,Cellular Signaling
更新于2025-09-23 15:21:01
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Benchmarking Digital Die-to-Die Channels in 2.5-D and 3-D Heterogeneous Integration Platforms
摘要： In this paper, compact circuit models and HSPICE simulations are used to benchmark die-to-die communication channels in 2.5-D and 3-D heterogeneous integration platforms. The delay, energy-per-bit, and bandwidth-density of the considered integration platforms are simulated and benchmarked. Compared to other 2.5-D integrated systems with a 1-mm interconnect length, heterogeneous interconnect stitching technology (HIST)-based 2.5-D integration shows a maximum latency and energy reduction of 6.2% and 15.1%, respectively. 3-D ICs show further performance enhancement compared to 2.5-D integration; the link latency and energy are approximately 19.4% and 48.0% smaller than those of HIST (1-mm wire) for through-silicon via (TSV)-based 3-D integration (75-μm TSV height). Next, the impacts of the physical I/O interconnect dimensions and device process technology scaling are evaluated and we observe that advanced process technologies must be integrated with smaller physical I/O dimensions and shorter wire lengths to attain full advantages of scaling. Finally, we consider the thermal impact of dense heterogeneous integration and investigate the thermal and electrical signaling tradeoffs in 2.5-D and 3-D integration.
关键词： Die-to-die interconnect,interposer and bridge-chip 2.5-D ICs,signaling
更新于2025-09-23 15:21:01