Skeletal muscle and bone interact at the level of mechanical loading through the application of force by muscles to the skeleton. Recently considerable focus has been placed on signaling ...factors/molecules produced by these two tissues that may act to modulate the function of the other tissue. We sought to determine if muscle and muscle-derived factors were essential to the osteocyte response to loading. Botox® induced muscle paralysis was used to investigate the role of muscle contraction during in vivo tibia compression loading. 5–6 month-old female TOPGAL mice had their right hindlimb muscles surrounding the tibia injected with either BOTOX® or saline. At four days post injections when muscle paralysis peaked, the right tibia was subjected to a single session of in vivo compression loading at ∼2600 με. At 24 h post-load we observed a 2.5-fold increase in β-catenin signaling in osteocytes in the tibias of the saline injected mice, whereas loading of tibias from Botox® injected mice failed to active β-catenin signaling in osteocytes. This suggests that active muscle contraction produces a factor(s) that is necessary for or conditions the osteocyte's ability to respond to load. To further investigate the role of muscle derived factors, MLO-Y4 osteocyte-like cells and a luciferase based β-catenin reporter (TOPflash-MLO-Y4) cell line we developed were treated with conditioned media (CM) from C2C12 myoblasts (MB) and myotubes (MT) and ex vivo contracted Extensor Digitorum Longus (EDL) and Soleus (Sol) muscles under static or loading conditions using fluid flow shear stress (FFSS). 10 % C2C12 myotube CM, but not myoblast or NIH3T3 fibroblast cells CM, induced a rapid activation of the Akt signaling pathway, peaking at 15 min and returning to baseline by 1–2 h under static conditions. FFSS applied to MLO-Y4 cells for 2 h in the presence of 10 % MT-CM resulted in a 6–8 fold increase in pAkt compared to a 3–4 fold increase under control or when exposed to 10 % MB-CM. A similar response was observed in the presence of 10 % EDL-CM, but not in the presence of 10 % Sol-CM. TOPflash-MLO-Y4 cells were treated with 10 ng/ml Wnt3a in the presence or absence of MT-CM. While MT-CM resulted in a 2-fold activation and Wnt3a produced a 10-fold activation, the combination of MT-CM + Wnt3a resulted in a 25-fold activation of β-catenin signaling, implying a synergistic effect of factors in MT-CM with Wnt3a. These data provide clear evidence that specific muscles and myotubes produce factors that alter important signaling pathways involved in the response of osteocytes to mechanical load. These data strongly suggest that beyond mechanical loading there is a molecular coupling of muscle and bone.
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•Muscle paraylysis prevents load-induced osteocyte β-catenin signaling.•Contracted EDL muscle produces factor(s) that induce β-catenin signalning.•C2C12 myotubes factor(s) synergize with Wnt3a to induce β-catenin signaling.•A luciferase based MLO-Y4 β-catenin reporter cell line was developed.
ZIF-8 (Z8), ZIF-67 (Z67), and ZMix, a Zn/Co bimetallic zeolitic imidazolate framework (ZIF), were synthesized and doped with tetrabutylammonium hydroxide (ZIFsT). The obtained powders were used as ...fillers for polyetherimide (PEI) at a concentration of 20wt %. The presence of the three ZIFsT in the polymeric matrix enhanced proton transport relative to that observed for PEI or ZIFs alone. The real and imaginary parts of the complex conductivity were obtained for each of the six materials, and the temperature and frequency dependence of the real part was analyzed. The results at different temperatures show that the dc-conductivity are about three orders of magnitude higher for the doped ZIFsT materials than for the PEI/ZIFsT membranes. In addition, the conductivity of the PEI/ZIFsT membranes increases five or six times when the temperature is changed from 25°C to 55°C. For these materials, the conductivity measurements have a linear dependency with frequency, which allowed for the creation of a master curve. It was also found that the PEI/ZMixT membrane activation energy is four times smaller than that of PEI/Z8T membranes and five times smaller than that of PEI/Z67T. Similarly, the real and imaginary parts of the complex dielectric constant were obtained, and the tan δ was evaluated. Using this value, the diffusion coefficient and the charge carrier density were obtained. A discussion of the proton transport mechanism through the membrane is given, and a comparison of this work with those on similar electrolyte membranes is included.
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•The ionic pair of tetrabutylammonium hydroxide was introduced within the Z8, Z67 and ZMix.•Mixed matrix membrane of PEI/ZIFsT prepared using the modified ZIFs as fillers have been characterized.•The relative amount of host molecules in Z8, Z67 and ZMix was determined.•The local electric anisotropy characteristic of ZMix favors the amount of doping the TBAH salt.•Activation energies for ZMixTW fillers and PZMixTW membranes were 0.13 and 0.14eV, respectively.
It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling ...causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through upregulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix-remodeling enzymes. In human skin samples, stromal fields adjacent to multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer.
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► Mesenchymal loss of CSL/Notch results in field cancerization of the skin epithelium ► Protumorigenic consequences of CSL loss are linked to c-Jun/c-Fos upregulation ► Anti-inflammatory treatment counteracts the field cancerization phenotype ► UVA exposure alters DNA methylation to downregulate stromal Notch signaling
Mesenchymal loss of a Notch effector or downregulation of Notch signaling by UVA triggers oncogenesis in the overlying epidermis. Inflammation of the stroma precedes the spread of epithelial lesions across a patch of skin, and importantly, inhibiting this inflammatory response counteracts the spread of multifocal skin tumors.
We performed simulations of the interaction of a graphene layer with the surface of lithium niobate utilizing density functional theory and molecular dynamics at 300K and atmospheric pressure. We ...found that the graphene layer is physisorbed on the lithium niobate surface with an adsorption energy of -0.8205 eV/(carbon-atom). Subsequently, the energy band structure, the optical absorption and reflectivity of the new system were calculated. We found important changes in these physical properties with respect to the corresponding ones of a graphene layer and of a lithium niobate crystal.
Polymerization of styrenic monomers containing imidazolium subunits in the presence of crosslinking monomers and using ionic liquids (ILs) as porogenic agents provides composite materials with ...excellent mechanical properties and displaying conductivities that are in the same order of magnitude than those shown by bulk ILs. This approach allows the use of high crosslinking degrees and low IL-loadings without compromising the required properties of the resulting composites. Besides, no appreciable leaching of the bulk IL component is detected.
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•Imidazolium cations have been polymerized with styrenic monomers subunits for SILLPs.•No appreciable leaching of the bulk IL component is detected.•Conductivities observed near room temperature are almost identical to the ILs bulk values.•Effect of anion nature has been distinguished between VBIM NTf2 and BMIM Cl.
This paper introduces an intuitive and safe command approach for a quadrotor, where inertial and muscular gestures are used for semi-autonomous flight. A bracelet composed of gyroscopes, ...accelerometers, and electromyographic sensors is used to detect user gestures, then an algorithm is proposed to interpret the signals as flight commands. The main goal is to provide a wearable, easy-to-handle human–machine interface for users a to safely command this kind of vehicles, even for inexpert operators. Safety measures are incorporated in the scheme to further enhance the user’s experience. Experimental tests are performed to validate the proposal.
The present paper describes the use of a microfluidic system to synthesize carbon dots (Cdots) and their use as optical pH sensors. The synthesis is based on the thermal decomposition of ascorbic ...acid in dimethyl sulfoxide. The proposed microsystem is composed of a fluidic and a thermal platform, which enable proper control of synthesis variables. Uniform and monodispersed 3.3 nm-sized Cdots have been synthesized, the optical characterization of which showed their down/upconversion luminescence and colorimetric properties. The obtained Cdots have been used for pH detection with down and upconverison fluorescent properties as excitation sources. The naked eye or a photographic digital camera has also been implemented as detection systems with the hue parameter showing a linear pH range from 3.5 to 10.2. On the other hand, experiments on the cytotoxicity and permeability of the Cdots on human embryonic kidney cells revealed their adsorption on cells without causing any impact on the cellular morphology.
In this study, we present results of the electronic density of states (DOS) and bulk magnetic moment of iron (Fe), cobalt (Co) and their alloys (Fe
x
Co
1–
x
;
x
= 1.0, 0.95, …, 0.0). Density ...functional theory with the generalized gradient approximation was applied to obtain geometric and electronic properties. The methodology uses virtual crystal approximation, in conjunction with CASTEP module and the functionals PBE and PBESol of the molecular simulation program Material Studio. We optimized the geometry of the bulk (obtaining their lattice parameters), which the structure was used to determine the bulk magnetic moments. To determine the magnetic moment, we calculated the difference of the electronic DOS of the electrons with spin up and spin down. The geometric optimization and magnetic moment obtained in the present study are very similar to the experimental results, with a maximum error of 8%, which makes the present article interesting.
•Monolithic microreactor for high-temperature and high-pressure synthesis of nanomaterials.•Integration of fluidics, heating system and optical window for the monitoring of generated reaction ...product.•Processes intensification of new optical sensing and bioimaging probe nanomaterials.
This work describes the development of a fully integrated Low Temperature Co-fired Ceramic (LTCC) microreactor for the synthesis of carbon dots (CDots). The microreactor integrates fluidics, a heating resistor and an optical window for fluorescence imaging of the reaction progress in a monolithic, all ceramic device, ensuring homogeneous surface chemistry and physical properties. A pool of different CDots was synthesized at high temperature and pressure using a hydrothermal method, demonstrating the robustness of the microreactor. The synthesis was monitored by following the photoluminescence of the produced CDots, and the reaction conditions were optimized according to their Quantum Yield (QY) and the flow pattern inside the microchannel. The obtained CDots exhibited blue photoluminescence upon irradiation with UV light with QYs of up to 0.77. The CDots were screened as metal nanoprobes and bioimaging contrast agents.
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