GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway.

Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown of Grm2 resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused by Grm2 knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided in vivo and in vitro evidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.

Single-beam three-axis SERF atomic magnetometer based on coordinate system rotation.

We propose what we believe to be a new single-beam three-axis spin exchange relaxation free (SERF) vector atomic magnetometer scheme based on coordinate system deflection. A theoretical model for the system response under arbitrary angle deflection was established for the first time, and the system response at different angles was simulated and analyzed. The simulation results show that the system response increases in the direction of the non-sensitive axis and decreases in the direction of the sensitive axis as the deflection angle increases, and the two responses tend to be the same when the angle is deflected to 45-degrees. Experimental measurements were carried out at a deflection angle of 45-degrees and the results showed that the sensitivity of the magnetometer was 55fT/Hz1/2 in the x1-axis, 38fT/Hz1/2 in the y1-axis and 60fT/Hz1/2 in the z1-axis. This single-beam magnetometer can be used to construct a miniaturized and low-cost weak magnetic sensor, which is expected to be used for vector measurement of biomagnetism.

Ultra-small, low-cost, and simple-to-control PSP projector based on SLCD technology.

Demand for ultra-small, inexpensive, and high-accurate 3D shape measurement devices is growing rapidly, especially in the industrial and consumer electronics sectors. Phase shifting profilometry (PSP) is a powerful candidate due to its advantages of high accuracy, great resolution, and insensitivity to ambient light. As a key component in PSP, the projector used to generate the phase-shifting sinusoidal fringes must be ultra-small (several millimeters), low-cost, and simple to control. However, existing projection methods make it difficult to meet these requirements simultaneously. In this paper, we present a modern technique that can be used to fabricate the desired projector. A specifically designed device based on segmented liquid crystal display (SLCD) technology is used to display the projected patterns, and a cylindrical lens is used as the projection lens. The SLCD device can display four sets of specific filled binary patterns, each yielding a sinusoidal fringe, and all four sinusoidal fringes satisfy the four-step phase shift relation. 3D shape measurement experiments verify the performance of the projector. Considering that the size of SLCD devices can be reduced to a few millimeters, the proposed technique can be easily used to manufacture ultra-small, low-cost, and simple-to-control PSP projectors.

Effects of system parameters on a single-beam synthetic gradiometer with a dual-cell structure.

We report a single-beam synthetic gradiometer operated in the spin-exchange-relaxation free (SERF) regime, using the structure of two separate atomic vapor cells spaced 2 cm apart. To improve the capability of the gradiometer in suppressing the common-mode magnetic field noise, we are aiming at investigating the effects of the system parameters on the gradiometer common-mode rejection ratio (CMRR). The mathematical expression for the relationship between the gradiometer CMRR and the two variables including the linewidth ratio and the pumping factor ratio is constructed for the first time, to our knowledge. This means that the CMRR can be optimized by controlling the linewidth and the pumping factor, which is easy to implement in the operation process. As a result, a CMRR of 246 is achieved and a gradiometer sensitivity of 4.5 fT/cm/Hz1/2 is also measured. This method provides a theoretical and experimental basis for the automated operation of gradiometers, and the gradiometer system performance can be tuned to a desired state by simply controlling the linewidth and the incident light intensity.

High-precision dynamic three-dimensional shape measurement of specular surfaces based on deep learning.

In order to solve the difficulty of traditional phase measuring deflectometry (PMD) in considering precision and speed, an orthogonal encoding PMD method based on deep learning is presented in this paper. We demonstrate for, what we believe to be, the first time that deep learning techniques can be combined with dynamic-PMD and can be used to reconstruct high-precision 3D shapes of specular surfaces from single-frame distorted orthogonal fringe patterns, enabling high-quality dynamic measurement of specular objects. The experimental results prove that the phase and shape information measured by the proposed method has high accuracy, almost reaching the results obtained by the ten-step phase-shifting method. And the proposed method also has excellent performance in dynamic experiments, which is of great significance to the development of optical measurement and fabrication areas.

A high-sensitivity single-light-source triaxial atomic magnetometer with double-cell and orthogonally pumped structure.

We first report a single-light-source orthogonally pumped triaxial atomic magnetometer with a double-cell structure. By using a beam splitter to equally allocate the pump beam, the proposed triaxial atomic magnetometer is responsive to magnetic fields in all three directions, and without sacrificing system sensitivity. The experimental results indicate that, the magnetometer achieves a sensitivity of 22 fT/Hz1/2 in x-direction with a 3-dB bandwidth of 22 Hz, a sensitivity of 23 fT/Hz1/2 in y-direction with a 3-dB bandwidth of 23 Hz, and a sensitivity of 21 fT/Hz1/2 in z-direction with a 3-dB bandwidth of 25 Hz. This magnetometer is useful for the applications that require the measurements of the three components of the magnetic field.

Thermal/Near-Infrared Light Dual-Responsive Reconfigurable and Recyclable Polythiourethane/CNT Composite with Simultaneously Enhanced Strength and Toughness.

Thermoset polymers cross-linked by dynamic covalent bonds are recyclable and reconfigurable based on solid-state plasticity, resulting in less waste and environmental pollution. However, most thermoset polymers previously reported show thermal-responsive solid-state plasticity, depending much on external conditions and not allowing for local shape modulation. Herein, the isocyanate modified carbon nanotubes (CNTs-NCO) are introduced into the polythiourethane (PCTU) network with multiple dynamic covalent bonds by in situ polymerization to prepare the composite with thermal/light dual-responsive solid-state plasticity, reconfigurability, and recyclability. The introduction of CNTs-NCO simultaneously strengthens and toughens the PCTU composite. Moreover, based on the photothermal properties and light-responsive solid-state plasticity, the PCTU/CNTs composite or bilayer sample can achieve complex permanent shape by locally precise shape regulation without affecting other parts. This work provides a simple and reliable method for preparing high-performance polymer composite with light-responsive solid-state plasticity, which may be applied in the fields of sensing and flexible electronics.

Deep learning-based Phase Measuring Deflectometry for single-shot 3D shape measurement and defect detection of specular objects.

Phase Measuring Deflectometry (PMD) and Structured-Light Modulation Analysis Technique (SMAT) perform effectively in shape and defect measurements of specular objects, but the difficulty of giving consideration to accuracy and speed has also restricted the further development and application of them. Inspired by recent successes of deep learning techniques for computational imaging, we demonstrate for the first time that deep learning techniques can be used to recover high-precision modulation distributions of specular surfaces from a single-frame fringe pattern under SMAT, enabling fast and high-quality defect detection of specular surfaces. This method can also be applied to recover higher-precision phase distributions of specular surfaces from a single-frame fringe pattern under PMD, so as to realize the 3D shape measurement. In this paper, we combine depthwise separable convolution, residual structure and U-Net to build an improved U-Net network. The experimental results prove that the method has excellent performance in the phase and modulation retrieval of specular surfaces, which almost reach the accuracy of the results obtained by ten-step phase-shifting method.

Modeling and optimization of cascaded lasing in a holmium doped fluoride fiber laser with efficient output at 3.92†µm.

In this paper, we investigate the output performance of a continuous-wave Ho3+-doped fluoride fiber laser operating at 3.92 µm from the 5I5 → 5I6 transition of Ho3+ using numerical simulation. A double-clad Ho3+-doped fluoroindate fiber with a doping concentration of 10.0 mol.% is assumed, with direct pumping at 888 nm. We propose simultaneous lasing on the 5I6 → 5I7 transition to enhance the slope efficiency while reducing the threshold and heat accumulation. Simulation results indicate that a slope efficiency of 17% and a threshold of 2.5 W can be obtained using a 9 cm-long fiber. Moreover, with the heat accumulation reduced by >40%, watt level laser output can be achieved in this cascade system at room temperature without the gain fiber being damaged by heat accumulation. The theoretical maximum output power of 1.27 W is 6 times higher than the highest reported value (197 mW), which is limited by the fiber damage due to excess heat load.

Structured-light modulation analysis technique for contamination and defect detection of specular surfaces and transparent objects.

With the rapid development of electronic industry, higher and higher requirements are placed on the surface quality of optical components in electronic devices. Structured-Light Modulation Analysis Technique (SMAT) was recently proposed to detect the contamination and defects on specular surfaces. In this paper, the proposed mechanisms and mathematical models of SMAT are analyzed and established based on the theory of photometry and the optical characteristics of contamination and defects for the first time. What's more, a novel transmission system adopting SMAT is especially designed for the defect detection of transparent objects. For both reflection and transmission system, simulations and experiments were conducted, and comparative studies with uniform planar illumination were also carried out. Simulations on the influence of incident light source region showed that SMAT can eliminate the interference of ambient light while uniform planar illumination technique cannot. Experiments on samples with specular surface and transparent material demonstrated that the modulation values at the contamination and defects are much less than that at clean and intact place, and defects and contaminations were clearly distinguished based on SMAT, while they were almost indiscernible with uniform planar illumination. Therefore, SMAT can be applied to the whole-field inspection of optical components in industrial environments.

Decreased CD1d level is associated with CD86 over-expression in B cells from systemic lupus erythematosus.

The disorder of B cells is one of the hallmarks of systemic lupus erythematosus (SLE). The activation state indicated by CD86 of B cells from SLE is well known, while the defect of regulatory B cells mediated by CD1d is also responsible for the process of SLE. In the present study, we focused on the relationship between B cell activation mediated by CD86 and B cell regulatory function mediated by CD1d. Our results showed that the level of CD1d in B cells was decreased during the early stages of B6.MRLlpr SLE mice and imiquimod-treated (IMQ-treated) mice, while the level of CD86 was significantly increased at the late stage. Moreover, the expression of CD1d showed a significantly negative correlation with CD86 level in B cells from IMQ-treated mice (r = -05741; P = 0.0022), B6.MRLlpr mice (r = -0.7091; P = 0.0268), and SLE patients (r = -0.4125; P = 0.0404). The in vivo and in vitro experiments with splenocytes demonstrated that CD1d signaling pathway could inhibit toll-like receptor 7 (TLR7)-induced CD86 expression of B cells. Further studies showed that this relationship also affected antibody production. Thus, our results confirmed the association of CD1d and CD86 levels in B cells from SLE, and demonstrated the importance to preserve the immunoregulatory function of B cells mediated by CD1d in the progression of SLE.

Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice.

CONTEXT: The natural polyphenolic compound curcumin has been proved to modulate innate immune responses and possess anti-inflammatory properties. Nevertheless, the mechanism remains poorly understood, particularly regarding curcumin-regulated miRNAs under inflammatory response. OBJECTIVE: This study investigates the role of miRNA-155 in the effects of curcumin on inflammatory response in cell and a mouse model. MATERIALS AND METHODS: The anti-inflammatory activity of curcumin (5, 10 and 15 µM, 2 h) in lipopolysaccharide (LPS, 200 ng/mL)-induced cells were measured by quantitative PCR. The animals were treated orally by 20 mg/kg curcumin for 3 days before an LPS intraperitoneal injection (10 mg/kg, 16 h). MicroRNA (miRNA) expression and the underlying molecular mechanisms were assessed using transfection technique and western blotting. RESULTS AND DISCUSSION: Curcumin efficiently inhibited LPS-induced cytokines (TNF-α, IL-6) and microRNA-155 (miR-155) expression (p < 0.05) without affecting the normally growth of Raw264.7 and THP-1 cells (IC50 21.8 and 22.3 µM at 48 h, respectively). Moreover, the levels of cytokines were suppressed by curcumin in miR-155 mimics transfected cells (p < 0.05). A blockade of PI3K/AKT signalling pathways resulted in a decreased level of miR-155 (p < 0.05). Curcumin effectively protected mice from sepsis as evidenced by decreasing histological damage, reducing AST (352.0 vs 279.3 U/L), BUN (14.8 vs 10.8 mmol/L) levels and the proportion of macrophages in spleen (31.1% vs 13.5%). MicroRNA-155 level and cytokines were also reduced in curcumin-treated mice (p < 0.05). CONCLUSIONS: Curcumin's ability to suppress LPS-induced inflammatory response may be due to the inhibition of miR-155.

A carrier removal method in phase measuring deflectometry based on the analytical carrier phase description.

In phase measuring deflectometry (PMD), a camera observes a sinusoidal fringe pattern via the surface of a specular object under test. Any slope variations of the surface lead to distortions of the observed pattern. Without height-angle ambiguity, carrier removal process is adopted to evaluate the variation of surface slope from phase distribution when a quasi-plane is measured. However, in the usual measurement system, the carrier phase will be nonlinear due to the restrictions of system geometries. In this paper, based on the analytical carrier phase description in PMD, a carrier removal method is proposed to remove the nonlinear carrier phase. Both the theoretical analysis and the experiment results are presented. By comparison with reference-subtraction method and series-expansion method, this proposed method can achieve carrier removal process with only the measurement of one single object, as well as high accuracy and time-saving.

A study on carrier phase distortion in phase measuring deflectometry with non-telecentric imaging.

In phase measuring deflectometry (PMD), the fringe pattern deformed according to slope deviation of a specular surface is digitized employing a phase-shift technique. Without height-angle ambiguity, carrier-removal process is adopted to evaluate the variation of surface slope from phase distribution when a quasi-plane is measured. However, the difficulty lies in the fact that the nonlinearity is generally contained in the carrier frequency due to the restrictions of system geometries. This paper investigates nonlinear carrier components introduced by the generalized imaging process in PMD. Furthermore, the analytical expression of carrier components in PMD is presented for the first time. The presented analytical form of carrier components can be extended to analyze and describe various effects of system parameters on carrier distortion. Assuming a pinhole perspective model, carrier phase distribution of arbitrary geometric arrangement is modeled as a function of spatial variables by exploring ray tracing method. As shown by simulation and experimental results, the carrier distortion is greatly affected by non-telecentric camera operation. Experimental results on the basis of reference subtraction technique further demonstrate that restrictions on reflection system geometry can be eliminated when the carrier phase is removed elaborately.

Characterization of the phase modulation property of a free-space electro-optic modulator by interframe intensity correlation matrix.

Characterization of a phase modulator or phase shifter has always been an integral part of phase-modulating or phase-adjusting applications. We propose a simplified approach to characterize a phase modulator by investigating the performance of phase shifts from grabbed interferograms using the phase extraction method. After reviewing some phase analysis techniques, the interframe intensity correlation (IIC) matrix method is introduced to the investigation. The proposed strategy is illustrated by the measurement of a free-space electro-optic modulator (EOM). Placing the modulator in one arm of a Michelson interferometer, the global phase shifts are estimated by the IIC method from the phase-stepped interferograms. Experimental results demonstrate the tested EOM has a phase modulation response of at least 2π rad with a π/20 rad modulation precision for λ=1064 nm. In addition, our method is applicable to various types of phase modulator or phase shifter calibration, e.g., electro-optic phase modulator, spatial light modulator, or piezoelectric transducer (PZT).

Involvement of LIN28A in Wnt-dependent regulation of hippocampal neurogenesis in the aging brain.

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein LIN28A remained existent in neural progenitor cells and granule neurons in the adult hippocampus and that it decreased with aging. Lin28a knockout inhibited the responsiveness of neural progenitor cells to niche Wnt agonists and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that LIN28A regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis and related cognitive functions.

A Protocol for Immunohistochemistry and RNA In-situ Distribution within Early Drosophila Embryo.

Calcium induced calcium release signaling (CICR) plays a critical role in many biological processes. Every cellular activity from cell proliferation and apoptosis, development and ageing, to neuronal synaptic plasticity and regeneration have been associated with Ryanodine receptors (RyRs). Despite the importance of calcium signaling, the exact mechanism of its function in early development is unclear. As an organism with a short gestational period, the embryos of Drosophila melanogaster are prime study subjects for investigating the distribution and localization of CICR associated proteins and their regulators during development. However, because of their lipid-rich embryos and chitin-rich chorion, their utility is limited by the difficulty of mounting embryos on glass surfaces. In this work, we introduce a practical protocol that significantly enhances the attachment of Drosophila embryo onto slides and detail methods for successful histochemistry, immunohistochemistry, and in-situ hybridization. The chrome alum gelatin slide-coating method and embryo pre-embedding method dramatically increases the yield in studying Drosophila embryo protein and RNA expression. To demonstrate this approach, we studied DmFKBP12/Calstabin, a well-known regulator of RyR during early embryonic development of Drosophila melanogaster. We identified DmFKBP12 in as early as the syncytial blastoderm stage and report the dynamic expression pattern of DmFKBP12 during development: initially as an evenly distributed protein in the syncytial blastoderm, then preliminarily localizing to the basement layer of the cortex during cellular blastoderm, before distributing in the primitive neuronal and digestion architecture during the three-gem layer phase in early gastrulation. This distribution may explain the critical role RyR plays in the vital organ systems that originate in from these layers: the suboesophageal and supraesophageal ganglion, ventral nervous system, and musculoskeletal system.

MG53, A Tissue Repair Protein with Broad Applications in Regenerative Medicine.

Under natural conditions, injured cells can be repaired rapidly through inherent biological processes. However, in the case of diabetes, cardiovascular disease, muscular dystrophy, and other degenerative conditions, the natural repair process is impaired. Repair of injury to the cell membrane is an important aspect of physiology. Inadequate membrane repair function is implicated in the pathophysiology of many human disorders. Recent studies show that Mitsugumin 53 (MG53), a TRIM family protein, plays a key role in repairing cell membrane damage and facilitating tissue regeneration. Clarifying the role of MG53 and its molecular mechanism are important for the application of MG53 in regenerative medicine. In this review, we analyze current research dissecting MG53's function in cell membrane repair and tissue regeneration, and highlight the development of recombinant human MG53 protein as a potential therapeutic agent to repair multiple-organ injuries.

Selective delignification of poplar wood with a newly isolated white-rot basidiomycete Peniophora incarnata T-7 by submerged fermentation to enhance saccharification.

BACKGROUND: Pretreatment is a critical step required for efficient conversion of woody biomass into biofuels and platform chemicals. Fungal pretreatment is regarded as one of the most promising technology for woody biomass conversion but remains challenging for industrial application. The exploration of potential fungus strain with high efficient delignification and less processing time for woody biomass pretreatment will be valuable for development of biorefinery industry. Here, a newly isolated white-rot basidiomycete Peniophora incarnate T-7 was employed for poplar wood pretreatment. RESULTS: The chemical component analysis showed that cellulose, hemicellulose and lignin from poplar wood declined by 16%, 48% and 70%, respectively, after 7 days submerged fermentation by P. incarnate T-7. Enzymatic saccharification analysis revealed that the maximum yields of glucose and xylose from 7 days of P. incarnate T-7 treated poplar wood reached 33.4% and 27.6%, respectively, both of which were enhanced by sevenfold relative to the untreated group. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD) and pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) characterization confirmed that lignocellulosic structure of poplar wood was largely broken by P. incarnate T-7, including delignification and de-crystalline of cellulose. Meanwhile, lignin component of poplar wood was selectively degraded by P. incarnate T-7, and G-type unit of lignin was preferentially attacked by the strain. Furthermore, quantitative proteomic analysis revealed that a considerable amount of lignocellulolytic enzymes were detected in the secretory proteins of P. incarnate T-7, especially with high abundance of lignin-degrading enzymes and hemicellulases. Combination of quantitative proteomic with transcriptomic analysis results showed that most of those lignocellulolytic enzymes were highly upregulated on poplar wood substrate compared to glucose substrate. CONCLUSIONS: This study showed that P. incarnate T-7 could selectively delignify poplar wood by submerged fermentation with short time of 7 days, which greatly improved its enzymatic saccharification efficiency. Our results suggested that P. incarnate T-7 might be a promising candidate for industrial woody biomass pretreatment.

Elucidation of ligninolysis mechanism of a newly isolated white-rot basidiomycete Trametes hirsuta X-13.

BACKGROUND: Lignin is a complex aromatic heteropolymer comprising 15-30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated. RESULTS: The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography-mass spectrometry (GC-MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography-mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical Cα-Cß breakage, the cleavage of lignin interunit linkages of ß-ß might also occur by T. hirsuta X-13. CONCLUSIONS: This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies.