CGRP Regulates the Age-Related Switch Between Osteoblast and Adipocyte Differentiation

Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss

Pathogenic Pseudorabies Virus, China, 2012

In 2012, an unprecedented large-scale outbreak of disease in pigs in China caused great economic losses to the swine industry. Isolates from pseudorabies virus epidemics in swine herds were characterized. Evidence confirmed that the pathogenic pseudorabies virus was the etiologic agent of this epidemic

High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination

We thank Elena Solomaha for advice on SPR experiments, Angela Hayes for clerical support, Christina Helms and Lori Garman for technical assistance, Gillian M. Air for providing influenza viruses; Linda F. Thompson for early involvement in the study and Meghan Sullivan, Irvin Ho and Sarah F. Andrews for helpful comments on the manuscript.Breakdown of B cell tolerance is a cardinal feature of systemic lupus erythematosus (SLE). Increased numbers of autoreactive mature naïve B cells have been described in SLE patients and autoantibodies have been shown to arise from autoreactive and non-autoreactive precursors. How these defects, in the regulation of B cell tolerance and selection, influence germinal center (GC) reactions that are directed towards foreign antigens has yet to be investigated. Here, we examined the characteristics of post-GC foreign antigen-specific B cells from SLE patients and healthy controls by analyzing monoclonal antibodies generated from plasmablasts induced specifically by influenza vaccination. We report that many of the SLE patients had anti-influenza antibodies with higher binding affinity and neutralization capacity than those from controls. Although overall frequencies of autoreactivity in the influenza-specific plasmablasts were similar for SLE patients and controls, the variable gene repertoire of influenza-specific plasmablasts from SLE patients was altered, with increased usage of JH6 and long heavy chain CDR3 segments. We found that high affinity anti-influenza antibodies generally characterize the plasmablast responses of SLE patients with low levels of autoreactivity; however, certain exceptions were noted. The high-avidity antibody responses in SLE patients may also be correlated with cytokines that are abnormally expressed in lupus. These findings provide insights into the effects of dysregulated immunity on the quality of antibody responses following influenza vaccination and further our understanding of the underlying abnormalities of lupus.Yeshttp://www.plosone.org/static/editorial#pee

6Ds-HLM: Hierarchical models of road traffic crash influencing factor analysis considering the urban built environment of intersection visibility

Road traffic safety issues pose a serious threat to urban health, and how the built environment affects traffic crashes has been hotly discussed. However, there are limitations in the selection of built environment factors according to the classic 5Ds system in most previous studies. Few studies have considered the influence exerted by visibility factors in intersection level and road diversity at the community level on traffic crashes, and the multi-level structure of crash data may be ignored. Therefore, the proposed visibility analysis method considering visible triangles and visual sensitivity is used to quantify the visual environment features of the intersections. Based on the proposed six-dimensional factors (6Ds) of the built environment (considering the intersection visibility degree and road diversity) and the hierarchical linear model (HLM), this paper proposes the 6Ds-HLM framework to analyze how road traffic crashes are influenced by the built environment factors. The results show that (1) the full model of the proposed 6Ds-HLM which contained the variables of intersection level and community level considering road diversity and the cross-level interactive effect performed best. (2) Interactive effects between intersection visibility and community built environment are founded, and significant 6Ds variables are identified using HLM: a) There was a positive cross-effect between intervisibility and road diversity. The viewshed area of the middle visual sensitive region also presented significant positive cross effects with traffic congestion speed, entertainment venue density, and road diversity. b) There was a significant negative cross-effect between the viewshed area of the middle visual sensitive region and school density

Exploring the Influences of Point-of-Interest on Traffic Crashes during Weekdays and Weekends via Multi-Scale Geographically Weighted Regression

Some studies on the impact of traditional land use factors on traffic crashes do not take into account the limitations of spatial heterogeneity and spatial scale. To overcome these limitations this study presents a systematic method based on multi-scale geographically weighted regression (MGWR), which considers spatial heterogeneity and spatial scale differences of different influencing factors, to explore the influence of reclassified points-of-interest (POI) on traffic crashes occurring on weekdays and weekends. Experiments were conducted on 442 communities in Hankou, Wuhan, and the performance of the proposed method was compared against traditional methods based on ordinary least squares (OLS), spatial lag model (SLM), spatial error model (SEM), and geographically weighted regression (GWR). The experiments show that the proposed method yielded the best fitness of models and more accurate model results of local coefficient estimates. The highlights of the results are as follows: There are differences in the scale of the predictor variables. Residential POI, scenic POI, and transportation POI have a global effect on traffic crashes. Commercial service POI and industrial POI affects traffic crashes at the regional scale, while public service POI affects crashes at the local scale. The local coefficient estimates from residential POI and scenic POI have little impact on traffic crashes. During weekdays, more transportation POI in the entire study area leads to more traffic crashes. While on weekends, transportation POI has a significant positive effect on crashes only in some communities. The local coefficient estimates for industrial POI vary at different periods. Commercial service POI and public service POI may increase the risk of crashes in some communities, which can be observed on weekdays and weekends. Exploring the influence of POI on traffic crashes at different periods is helpful for traffic management strategies and in reducing traffic crashes

NMR resonance assignment and structure prediction of the C-terminal domain of the microtubule end-binding protein 3.

End-binding proteins (EBs) associate with the growing microtubule plus ends to regulate microtubule dynamics as well as the interaction with intracellular structures. EB3 contributes to pathological vascular leakage through interacting with the inositol 1,4,5-trisphosphate receptor 3 (IP3R3), a calcium channel located at the endoplasmic reticulum membrane. The C-terminal domain of EB3 (residues 200-281) is functionally important for this interaction because it contains the effector binding sites, a prerequisite for EB3 activity and specificity. Structural data for this domain is limited. Here, we report the backbone chemical shift assignments for the human EB3 C-terminal domain and computationally explore its EB3 conformations. Backbone assignments, along with computational models, will allow future investigation of EB3 structural dynamics, interactions with effectors, and will facilitate the development of novel EB3 inhibitors

Distributed Partial Discharge Locating and Detecting Scheme Based on Optical Fiber Rayleigh Backscattering Light Interference

Optical fiber sensors are used for partial discharge detection in many applications due their advantage of strong anti-electromagnetic interference capability. Multi-point distributed partial discharge detection and location are important for electrical equipment. In this paper, a distributed partial discharge location and detection scheme based on optical fiber Rayleigh backscattering light interference is experimentally demonstrated. At the same time, the location and extraction algorithm is used to demodulate the partial discharge signal; furthermore, the high-pass filter is used to reduce the system low-frequency noise and environment noise. It is clear that the proposed system can detect a partial discharge signal generated by metal needle sensitivity, and the detectable frequency range is 0–2.5 kHz. We carried out 10 locating tests for two sensing units, the experimental results show that the maximum location error is 1.0 m, and the maximum standard deviation is 0.3795. At same time, the signal-to-noise ratio (SNR) of sensing unit 1 and sensing unit 2 are greatly improved after demodulation, which are 39.7 and 38.8, respectively. This provides a new method for a multipoint-distributed optical fiber sensor used for detecting and locating a long-distance electrical equipment partial discharge signal

Distributed Partial Discharge Locating and Detecting Scheme Based on Optical Fiber Rayleigh Backscattering Light Interference

Optical fiber sensors are used for partial discharge detection in many applications due their advantage of strong anti-electromagnetic interference capability. Multi-point distributed partial discharge detection and location are important for electrical equipment. In this paper, a distributed partial discharge location and detection scheme based on optical fiber Rayleigh backscattering light interference is experimentally demonstrated. At the same time, the location and extraction algorithm is used to demodulate the partial discharge signal; furthermore, the high-pass filter is used to reduce the system low-frequency noise and environment noise. It is clear that the proposed system can detect a partial discharge signal generated by metal needle sensitivity, and the detectable frequency range is 0–2.5 kHz. We carried out 10 locating tests for two sensing units, the experimental results show that the maximum location error is 1.0 m, and the maximum standard deviation is 0.3795. At same time, the signal-to-noise ratio (SNR) of sensing unit 1 and sensing unit 2 are greatly improved after demodulation, which are 39.7 and 38.8, respectively. This provides a new method for a multipoint-distributed optical fiber sensor used for detecting and locating a long-distance electrical equipment partial discharge signal