Selective inactivation of Stat3 in osteoclasts affect bone mass differently in female and male mice

poster abstractSignal Transducer and Activator of Transcription 3 (Stat3) is activated by the binding of various cytokines to their receptors, such as IL-6. Previous studies have revealed that conditional knockouts of Stat3 in osteoblasts and osteocytes cause a decrease in bone mineral density and strength. To study the role of Stat3 in osteoclasts, osteoclast- specific knockout mice were created using cre-lox recombination. Bone mineral density (BMD) and bone mineral content (BMC) were calculated for femurs and the fourth lumbar vertebra (L4) of 8 weeks old mice. Analysis revealed a decrease in BMD of femurs of osteoclast-selective Stat3 knockout (KOOc-Stat3) mice compared to their littermate control (p<0.05). There was also a decrease in BMC of the femurs of KOOc-Stat3 mice compared to the littermate controls (p<0.05). Analysis of μCT data from trabecular bone in the distal femur showed significant decreases in trabecular number and bone volume/tissue volume in both male and female KOOc-Stat3 mice. Trabecular separation was increased in male and female KOOc-Stat3 mice. Bone histomorphometry at the distal femur revealed a significant decrease in bone formation rate in males and females KOOc-Stat3 mice compared to the littermate controls. Osteoclast number identified by tartrate resistant acid phosphatase (TRAP) stain in female KOOc-Stat3 mice was significantly deficient from their control. These data suggest that inactivation of Stat3 in osteoclasts influences bone metabolism through both osteoblasts and osteoclasts. Knockout of Stat3 in either cell type leads to decreases in bone strength, making Stat3 a good drug target for treatment of diseases such as osteoporosis

Chaotic motion of scalar particle coupling to Chern-Simons invariant in Kerr black hole spacetime

We present firstly the equation of motion for the test scalar particle coupling to the Chern-Simons invariant in Kerr black hole spacetime by the short-wave approximation. We have analyzed the dynamical behaviors of the test coupled particles by applying techniques including Poincar\'e sections, fast Lyapunov exponent indicator, bifurcation diagram and basins of attraction. It is shown that there exists chaotic phenomenon in the motion of scalar particle interacted with the Chern-Simons invariant in a Kerr black hole spacetime. With the increase of the coupling strength, the motion of the coupled particles for the chosen parameters first undergoes a series of transitions betweens chaotic motion and regular motion and then falls into horizon or escapes to spatial infinity. Thus, the coupling between scalar particle and Chern-Simons invariant yields the richer dynamical behavior of scalar particle in a Kerr black hole spacetime.Comment: 21 pages, 11 figures, Accepted for publication in EPJ

Maxwell quasinormal modes on a global monopole Schwarzschild-anti-de Sitter black hole with Robin boundary conditions

We generalize our previous studies on the Maxwell quasinormal modes around Schwarzschild-anti-de-Sitter black holes with Robin type vanishing energy flux boundary conditions, by adding a global monopole on the background. We first formulate the Maxwell equations both in the Regge-Wheeler-Zerilli and in the Teukolsky formalisms and derive, based on the vanishing energy flux principle, two boundary conditions in each formalism. The Maxwell equations are then solved analytically in pure anti-de Sitter spacetimes with a global monopole, and two different normal modes are obtained due to the existence of the monopole parameter. In the small black hole and low frequency approximations, the Maxwell quasinormal modes are solved perturbatively on top of normal modes by using an asymptotic matching method, while beyond the aforementioned approximation, the Maxwell quasinormal modes are obtained numerically. We analyze the Maxwell quasinormal spectrum by varying the angular momentum quantum number $\ell$, the overtone number $N$, and in particular, the monopole parameter $8\pi\eta^2$. We show explicitly, through calculating quasinormal frequencies with both boundary conditions, that the global monopole produces the repulsive force.Comment: 10 pages, 5 figures, to appear in EPJ

AMPLE: An Adaptive Multiple Path Loss Exponent Radio Propagation Model Considering Environmental Factors

We present AMPLE -- a novel multiple path loss exponent (PLE) radio propagation model that can adapt to different environmental factors. The proposed model aims at accurately predicting path loss with low computational complexity considering environmental factors. In the proposed model, the scenario under consideration is classified into regions from a raster map, and each type of region is assigned with a PLE. The path loss is then computed based on a direct path between the transmitter (Tx) and receiver (Rx), which records the intersected regions and the weighted region path loss. To regress the model, the parameters, including PLEs, are extracted via measurement and the region map. We also verify the model in a suburban area. To the best of our knowledge, this is the first time that a multi-slope model precisely maps PLEs and region types. Besides, this model can be integrated into map systems by creating a new path loss attribute for digital maps.Comment: This paper has been submitted to IEEE Transactions for possible publication

Optimal Repair Strategy Against Advanced Persistent Threats Under Time-Varying Networks

Advanced persistent threat (APT) is a kind of stealthy, sophisticated, and long-term cyberattack that has brought severe financial losses and critical infrastructure damages. Existing works mainly focus on APT defense under stable network topologies, while the problem under time-varying dynamic networks (e.g., vehicular networks) remains unexplored, which motivates our work. Besides, the spatiotemporal dynamics in defense resources, complex attackers' lateral movement behaviors, and lack of timely defense make APT defense a challenging issue under time-varying networks. In this paper, we propose a novel game-theoretical APT defense approach to promote real-time and optimal defense strategy-making under both periodic time-varying and general time-varying environments. Specifically, we first model the interactions between attackers and defenders in an APT process as a dynamic APT repair game, and then formulate the APT damage minimization problem as the precise prevention and control (PPAC) problem. To derive the optimal defense strategy under both latency and defense resource constraints, we further devise an online optimal control-based mechanism integrated with two backtracking-forward algorithms to fastly derive the near-optimal solution of the PPAC problem in real time. Extensive experiments are carried out, and the results demonstrate that our proposed scheme can efficiently obtain optimal defense strategy in 54481 ms under seven attack-defense interactions with 9.64$\%$ resource occupancy in stimulated periodic time-varying and general time-varying networks. Besides, even under static networks, our proposed scheme still outperforms existing representative APT defense approaches in terms of service stability and defense resource utilization

Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys

<p>Ischemic preconditioning (IPC) affords tissue protection in organs including kidneys; however, the underlying mechanism remains unclear. Here we demonstrate an important role of macroautophagy/autophagy (especially mitophagy) in the protective effect of IPC in kidneys. IPC induced autophagy in renal tubular cells in mice and suppressed subsequent renal ischemia-reperfusion injury (IRI). The protective effect of IPC was abolished by pharmacological inhibitors of autophagy and by the ablation of <i>Atg7</i> from kidney proximal tubules. Pretreatment with BECN1/Beclin1 peptide induced autophagy and protected against IRI. These results suggest the dependence of IPC protection on renal autophagy. During IPC, the mitophagy regulator PINK1 (PTEN induced putative kinase 1) was activated. Both IPC and BECN1 peptide enhanced mitolysosome formation during renal IRI in mitophagy reporter mice, suggesting that IPC may protect kidneys by activating mitophagy. We further established an in vitro model of IPC by inducing ‘chemical ischemia’ in kidney proximal tubular cells with carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Brief treatment with CCCP protected against subsequent injury in these cells and the protective effect was abrogated by autophagy inhibition. In vitro IPC increased mitophagosome formation, enhanced the delivery of mitophagosomes to lysosomes, and promoted the clearance of damaged mitochondria during subsequent CCCP treatment. IPC also suppressed mitochondrial depolarization, improved ATP production, and inhibited the generation of reactive oxygen species. Knockdown of <i>Pink1</i> suppressed mitophagy and reduced the cytoprotective effect of IPC. Together, these results suggest that autophagy, especially mitophagy, plays an important role in the protective effect of IPC.</p> <p><b>Abbreviations</b>: ACTB: actin, beta; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; BUN: blood urea nitrogen; CASP3: caspase 3; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; COX4I1: cytochrome c oxidase subunit 4I1; COX8: cytochrome c oxidase subunit 8; DAPI: 4ʹ,6-diamidino-2-phenylindole; DNM1L: dynamin 1 like; EGFP: enhanced green fluorescent protein; EM: electron microscopy; ER: endoplasmic reticulum; FC: floxed control; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; H-E: hematoxylin-eosin; HIF1A: hypoxia inducible factor 1 subunit alpha; HSPD1: heat shock protein family D (Hsp60) member 1; IMMT/MIC60: inner membrane mitochondrial protein; IPC: ischemic preconditioning; I-R: ischemia-reperfusion; IRI: ischemia-reperfusion injury; JC-1: 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ-tetraethylbenzimidazolylcarbocyanine iodide; KO: knockout; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; mito-QC: mito-quality control; mRFP: monomeric red fluorescent protein; NAC: N-acetylcysteine; PINK1: PTEN induced putative kinase 1; PPIB: peptidylprolyl isomerase B; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; RPTC: rat proximal tubular cells; SD: standard deviation; sIPC: simulated IPC; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling</p

White Matter Abnormalities in Major Depression: A Tract-Based Spatial Statistics and Rumination Study

Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS) method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected), findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected). The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD

Influence of the Friction Block Shape and Installation Angle of High-Speed Train Brakes on Brake Noise

Abstract In this study, experiments are conducted to evaluate the effects of friction block shapes and installation angles on the brake noise of high-speed trains on a customized small-scale brake dynamometer. Friction blocks in three different shapes (circle, triangle, and hexagon) and triangular/hexagonal friction blocks at different installation angles are used in the tests. The results indicate that the circular and triangular blocks exhibit low sound pressure with multiple harmonics, whereas the hexagonal friction block produces the highest sound pressure with a single dominant frequency. This difference is attributed to the high contact pressure and severe wear on the surface of the hexagonal friction block. Differences in the installation angle of the triangular/hexagonal friction blocks affect wear debris behavior, distribution of contact pressure, and contact state of the friction interface, consequently influencing noise performance.</jats:p

The limbic-prefrontal network modulated by electroacupuncture at CV4 and CV12

fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture\u27s modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation. Copyright © 2012 Jiliang Fang et al