Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth

Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.

BER Performance of FSO Communication System with Differential Signaling over Correlated Atmospheric Turbulence Fading

Free space optical(FSO) communication system with differential signaling possesses the advantage of requiring no channel state information and avoiding computational load or link throughput reduction compared to the systems with conventional receivers. In this work, we investigate bit error rate(BER) performance of this system over partially and fully correlated atmospheric turbulence fading. In order to conduct the above analysis, we obtain a probability density functions(PDF) of the channel fading on the differential signals and derive our instantaneous BER using differential signaling scheme. Based on these results, we develop two closed-form mathematical expressions for the average BER under fully correlated and partially correlated fading in the convergent infinite series confirmed by Cauchy’s ratio test. The accuracy of the derived BER expressions is demonstrated by the Monte Carlo simulations, and the analyses for the effects of the system parameters on the BER performance are provided.

Parameter Estimation of Multi-component Chirp Signal Based on Differential Evolution

Chirp signals show energy aggregation in the fractional Fourier domain(FrFD) w hich can be used to estimate the parameter of the signals. In this paper,a parameter estimation method for multi-component chirp signal w hich corrupted by w hite Gaussian noise is proposed based on the discrete fractional Fourier transform(DFrFT) and the differential evolution( DE) algorithm. The proposed algorithm uses the DE algorithm instead of the conventional fine search algorithm to detect the peak of the signals in the FrFD. The paper simulated the influence of the noise and the resolution of the proposed algorithm. The results of the simulation show the proposed method does not only improve the estimation accuracy of the peak coordinate,but also reduces time consuming.

Broad-Band All-Optical Wavelength Conversion of Differential Phase-Shift Keyed Signal Using an SOA-Based Nonlinear Polarization Switch

Broad-band all-optical wavelength conversion of differential phase-shift keyed （DPSK） signal is experimentally demonstrated. This scheme is composed of a one-bit delay interferometer demodulation stage followed by a semiconductor optical amplifier （SOA） based nonlinear polarization switch. A wavelength converter for the 10 G b/s DPSK signal is presented, which has a wide wavelength range of more than 30 nm. The converted signals experience small power penalties less than 1.4 dB compared with the original signal, at a bit error rate of 10-9. Additionally, the optical spectra, the measured waveforms and the open eye diagrams of the converted signals show a high quality wavelength conversion performance.

SIGNAL CONSTELLATIONS DESIGN FOR DIFFERENTIAL UNITARY SPACE-TIME IN MIMO-OFDM SYSTEM OVER FREQUENCY-SELECTIVE FADING CHANNELS

In this paper, the design of signal constellations parameters is studied for Differential Unitary Space-Time Modulation (DUSTM) based on the design criterion of maximizing the diversity product. Further, noninteger searching method for the signal constellation parameters design is proposed in order to get better codes. Experimental results show that under the different Doppler spread and data transmission rate, the proposed design performs better than the previous design using integer parameters in Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing (MIMO-OFDM) system over frequency-selective fading channels.

Neural differentiation from embryonic stem cells in vitro : An overview of the signaling pathways

Neurons derived from embryonic stem cells(ESCs) have gained great merit in both basic research and regenerative medicine. Here we review and summarize the signaling pathways that have been reported to be involved in the neuronal differentiation of ESCs,particularly those associated with in vitro differentiation. The inducers and pathways explored include retinoic acid, Wnt/b-catenin, transforming growth factor/bone morphogenetic protein, Notch, fibroblast growth factor, cytokine, Hedgehog, c-Jun N-terminal kinase/mitogen-activated protein kinase and others. Some other miscellaneous molecular factors that have been reported in the literature are also summarized and discussed. These include calcium, calcium receptor, calcineurin, estrogen receptor, Hox protein, ceramide, glycosaminioglycan, ginsenoside Rg1, opioids, two pore channel 2, nitric oxide, chemically defined medium, cellcell interactions, and physical stimuli. The interaction or crosstalk between these signaling pathways and factors will be explored. Elucidating these signals in detail should make a significant contribution to future progress in stem cell biology and allow, for example, better comparisons to be made between differentiation in vivo and in vitro. Of equal importance, a comprehensive understanding of the pathways that are involved in the development of neurons from ESCs in vitro will also accelerate their application as part of translational medicine.

YAP promotes osteogenesis and suppresses adipogenic differentiation by regulatingβ-catenin signaling

YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.

Compressed ghost imaging based on differential speckle patterns

We propose a compressed ghost imaging scheme based on differential speckle patterns,named CGI-DSP.In the scheme,a series of bucket detector signals are acquired when a series of random speckle patterns are employed to illuminate an unknown object.Then the differential speckle patterns(differential bucket detector signals)are obtained by taking the difference between present random speckle patterns(present bucket detector signals)and previous random speckle patterns(previous bucket detector signals).Finally,the image of object can be obtained directly by performing the compressed sensing algorithm on the differential speckle patterns and differential bucket detector signals.The experimental and simulated results reveal that CGI-DSP can improve the imaging quality and reduce the number of measurements comparing with the traditional compressed ghost imaging schemes because our scheme can remove the environmental illuminations efficiently.

Pterygium epithelium abnormal differentiation related to activation of extracellular signal-regulated kinase signaling pathway in vitro

AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes

Background:Tuberculosis is a leading cause of death worldwide.BCG is an effective vaccine,but not widely used in many parts of the world due to a variety of issues.Mycobacterium vaccae(M.vaccae)is another vaccine used in human subjects to prevent tuberculosis.In the current study,we investigated the potential mechanisms of M.vaccae vaccination by determining differentially expressed genes in mice infected with M.tuberculosis before and after M.vaccae vaccination.Methods:Three days after exposure to M.tuberculosis H37 Rv strain(5×10~5 CFU),adult BALB/c mice randomly received either M.vaccae vaccine(22.5μg)or vehicle via intramuscular injection(n=8).Booster immunization was conducted 14 and 28 days after the primary immunization.Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.Results:M.vaccae vaccination provided protection against M.tuberculosis infection(most prominent in the lungs).We identified 2,326 upregulated and 2,221 downregulated genes in vaccinated mice.These changes could be mapped to a total of 123 signaling pathways(68 upregulated and 55 downregulated).Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3 K-Akt signaling pathway as most likely to be functional.Conclusions:M.vaccae vaccine provided good protection in mice against M.tuberculosis infection,via a highly complex set of molecular changes.Our findings may provide clue to guide development of more effective vaccine against tuberculosis.

Signaling involved in stem cell reprogramming and differentiation

Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have reve-aled that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell pro-gramming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review,the molecular interactions and signaling pathways related to stem cell differentiation are discussed.

RANKL-RANK signaling regulates osteoblast differentiation and bone formation

In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that

Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation

Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

HBP1 inhibits chicken preadipocyte differentiation by activating the STAT3 signaling via directly enhancing JAK2 expression

Obesity presents a serious threat to human health and broiler performance.The expansion of adipose tissue is mainly regulated by the differentiation of preadipocytes.The differentiation of preadipocytes is a complex biological process regulated by a variety of transcription factors and signaling pathways.Previous studies have shown that the transcription factor HMG-box protein 1(HBP1)can regulate the differentiation of mouse 3T3-L1 preadipocytes by activating the Wnt/β-catenin signaling pathway.However,it is unclear whether HBP1 involved in chicken preadipocyte differentiation and which signaling pathways it regulates.The aim of the current study was to explore the biological function and molecular regulatory mechanism of HBP1 in the differentiation of chicken preadipocytes.The expression patterns of chicken HBP1 in abdominal adipose tissue and during preadipocyte differentiation were analyzed by RT-qPCR and Western blot.The preadipocyte stably overexpressing HBP1 or knockout HBP1 and their control cell line were used to analyze the effect of HBP1 on preadipocyte differentiation by oil red O staining,RT-qPCR and Western blot.Cignal 45-Pathway Reporter Array was used to screen the signal pathways that HBP1 regulates in the differentiation of chicken preadipocytes.Chemical inhibitor and siRNA for signal transducer and activator of transcription 3(STAT3)were used to analyze the effect of STAT3 on preadipocyte differentiation.The preadipocyte stably overexpressing HBP1 was transfected by the siRNA of STAT3 or treated with a chemical inhibitor of STAT3 for the rescue experiment.The results of gene expression analysis showed that the expression of HBP1 was related to abdominal fat deposition and preadipocyte differentiation in chickens.The results of function gain and loss experiments indicated that overexpression/knockout of HBP1 in chicken preadipocytes could inhibit/promote(P<0.05)lipid droplet deposition and the expression of adipogenesis-related genes.Mechanismlly,HBP1 activates(P<0.05)the signal transducer and activator of transcription 3(STAT3)signaling pathway by targeting janus kinase 2(JAK2)transcription.The results of functional rescue experiments indicated that STAT3 signaling mediated the regulation of HBP1 on chicken preadipocyte differentiation.In conclusion,HBP1 inhibits chicken preadipocyte differentiation by activating the STAT3 signaling pathway via directly enhancing JAK2 expression.Our findings provided new insights for further analysis of the molecular genetic basis of chicken adipose tissue growth and development.

Differential-equation Filtering in Seismic Data Processing

Noise attenuation is necessary before and after stacking in the seismic data processing. We describe the filtering method based on differential equations, which transforms the filtering equations in the frequency domain or in the f-k domain back into the time or time-space domains, and use the finite-difference algorithm to solve the equations. The method does not require the seismic data being stationary; and the filtering parameters can vary at any temporal and spatial point. The application results of real data show that the method has a good processing quality.

Optical time-domain differentiation based on intensive differential group delay

An optical time-domain differentiation scheme is proposed and demonstrated based on the intensive differential group delay in a high birefringence fibre waveguide. Results show that the differentiation waveforms agree well with the mathematically calculated derivatives. Both error and efficiency will increase when the birefringence fibre becomes longer, and the error rises up more quickly while the efficiency approaches to a maximum of ~0.25. By using a 1-m birefringence fibre a lower error of ~0.26% is obtained with an efficiency of 1% for the first-order differentiation of 10-ps Gaussian optical pulses, and the high-order optical differentiation up to 4th order is achieved with an error less than 3%. Due to its compact structure being easy to integrate and cascade into photonic circuits, our scheme has great potential for ultrafast signal processing.

Inhibition of self-renewal and differentiation of HT-29 cells-derived cancer stem-like cells by scutellarin via Hedgehog signaling pathway

OBJECTIVE To investigate the inhibitory effect of scutellarin on the self-renewal and differentiation of HT-29 cells-derived cancer stem-like cells(HT-29CSC)in vitro and in vivo,and to explore its mechanism.METHODS The effect of scutellarin on the growth of HT-29CSC was determined by 3D Culture assay.The effect of scutellarin on growth and transformation of HT-29CSC was probed by soft agar colony formation assay.The effect of scutellarin on the differentiation of HT-29CSC was determined by serum induction differentiation assay in vitro.The effects of scutellarin on the expressions of marker gene Lgr5,target gene c-Myc,proliferation gene CK20 and Nanog gene were measured by quantitative real-time RT-PCR.Investigate the effect of scutellarin on the expression of c-Myc,Gli1,and Lgr5 protein by Western blotting.A subcutaneous xenograft model of colon cancer in nude mice was established and administered by intraperitoneal injection.The change of body weight and tumor size of nude mice were observed every two days.Investi⁃gate the effects of scutellarin on the growth of xenograft tumors in nude mice.The expression of CD133,Lgr5,Gli1,Ptch1,c-Myc,Ki67,CK20,Nanog gene in tumors were measured by quantitative real-time RT-PCR.The expression of c-Myc,Gli1,Lgr5,CD133,Ki67 protein were measured by Western blotting.RESULTS Scutellarin can inhibit the growth of HT-29CSC in 3D culture.Compared with the solvent control group,scutellarin can significantly inhibit the growth and transformation and differentiation of HT-29CSC in vitro(P<0.01).The expression levels of marker genes Lgr5,target gene c-Myc,proliferation gene CK20 and Nanog in HT-29CSC were down-regulated by scutellarin.Scutellarin can reduce the expression of c-Myc,Gli1,and Lgr5 protein in HT-29CSC.Scutellarin can inhibit the growth of colon cancer xenografts,lower CD133,Lgr5,Gli1,Ptch1,c-Myc,Ki67,CK20,and Nanog mRNA level of xenograft tumors,reduce the expression of c-Myc,Gli1,Lgr5,CD133,and Ki67 protein of xenograft tumors in nude mice.CONCLUSION Scutellarin,which is the main component of scutellaria barbata,can inhibit the differentiation of HT-29CSC and the mechanism is to inhibit the activity of Hedgehog signaling pathway.

How mesenchymal stem cells transform into adipocytes:Overview of the current understanding of adipogenic differentiation

Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

High Performance Bilinear Differential Preamplifier for BESⅢ Time-of-Flight System

A time-of-flight (TOF) detector has been used in the BESIII experiment to provide charged particle identification. In this paper, we present a novel high performance differential amplifier, which has been designed for amplifying the signals from the detectors. The preamplifier can amplify differential signals, which can help to eliminate the common mode pickup, and increase the signal-to-noise ratio (SNR). Bilinear gain is one of the features of this preamplifier, which greatly increases the dynamic range and avoids the dead time of the preamplifier. In order to describe the bilinear gain, a 4-parameter function is developed. And this 4-parameter function can also be used in the calibration of the time walk caused by the amplitude due to the bilinear gain. The preamplifier has a gain about 10V/V with a small signal and about 1.0V/V with a large signal. The rise time of the preamp is less than 2 ns.