Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

Trace-gas metabolic versatility of the facultative methanotroph Methylocella silvestris

The climate-active gas methane is generated both by biological processes and by thermogenic decomposition of fossil organic material, which forms methane and short-chain alkanes, principally ethane, propane and butane1, 2. In addition to natural sources, environments are exposed to anthropogenic inputs of all these gases from oil and gas extraction and distribution. The gases provide carbon and/or energy for a diverse range of microorganisms that can metabolize them in both anoxic3 and oxic zones. Aerobic methanotrophs, which can assimilate methane, have been considered to be entirely distinct from utilizers of short-chain alkanes, and studies of environments exposed to mixtures of methane and multi-carbon alkanes have assumed that disparate groups of microorganisms are responsible for the metabolism of these gases. Here we describe the mechanism by which a single bacterial strain, Methylocella silvestris, can use methane or propane as a carbon and energy source, documenting a methanotroph that can utilize a short-chain alkane as an alternative to methane. Furthermore, during growth on a mixture of these gases, efficient consumption of both gases occurred at the same time. Two soluble di-iron centre monooxygenase (SDIMO) gene clusters were identified and were found to be differentially expressed during bacterial growth on these gases, although both were required for efficient propane utilization. This report of a methanotroph expressing an additional SDIMO that seems to be uniquely involved in short-chain alkane metabolism suggests that such metabolic flexibility may be important in many environments where methane and short-chain alkanes co-occur

Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro

Extracellular ATP, signalling through P2 receptors, exerts well-documented effects on bone cells, inhibiting mineral deposition by osteoblasts and stimulating the formation and resorptive activity of osteoclasts. The aims of this study were to determine the potential osteotropic effects of adenosine, the hydrolysis product of ATP, on primary bone cells in vitro. We determined the effect of exogenous adenosine on (1) the growth, alkaline phosphatase (TNAP) activity and bone-forming ability of osteoblasts derived from the calvariae of neonatal rats and mice and the marrow of juvenile rats and (2) the formation and resorptive activity of osteoclasts from juvenile mouse marrow. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed marked differences in the expression of P1 receptors in osteoblasts from different sources. Whilst mRNA for the A1 and A2B receptors was expressed by all primary osteoblasts, A2A receptor expression was limited to rat bone marrow and mouse calvarial osteoblasts and the A3 receptor to rat bone marrow osteoblasts. We found that adenosine had no detectable effects on cell growth, TNAP activity or bone formation by rodent osteoblasts in vitro. The analogue 2-chloroadenosine, which is hydrolysed more slowly than adenosine, had no effects on rat or mouse calvarial osteoblasts but increased TNAP activity and bone formation by rat bone marrow osteoblasts by 30–50 % at a concentration of 1 μM. Osteoclasts were found to express the A2A, A2B and A3 receptors; however, neither adenosine (≤100 μM) nor 2-chloroadenosine (≤10 μM) had any effect on the formation or resorptive activity of mouse osteoclasts in vitro. These results suggest that adenosine, unlike ATP, is not a major signalling molecule in the bone

Lipid-Induced Toxicity Stimulates Hepatocytes to Release Angiogenic Microparticles That Require Vanin-1 for Uptake by Endothelial Cells.

Angiogenesis is a key pathological feature of experimental and human steatohepatitis, a common chronic liver disease that is associated with obesity. We demonstrated that hepatocytes generated a type of membrane-bound vesicle, microparticles, in response to conditions that mimicked the lipid accumulation that occurs in the liver in some forms of steatohepatitis and that these microparticles promoted angiogenesis. When applied to an endothelial cell line, medium conditioned by murine hepatocytes or a human hepatocyte cell line exposed to saturated free fatty acids induced migration and tube formation, two processes required for angiogenesis. Medium from hepatocytes in which caspase 3 was inhibited or medium in which the microparticles were removed by ultracentrifugation lacked proangiogenic activity. Isolated hepatocyte-derived microparticles induced migration and tube formation of an endothelial cell line in vitro and angiogenesis in mice, processes that depended on internalization of microparticles. Microparticle internalization required the interaction of the ectoenzyme Vanin-1 (VNN1), an abundant surface protein on the microparticles, with lipid raft domains of endothelial cells. Large quantities of hepatocyte-derived microparticles were detected in the blood of mice with diet-induced steatohepatitis, and microparticle quantity correlated with disease severity. Genetic ablation of caspase 3 or RNA interference directed against VNN1 protected mice from steatohepatitis-induced pathological angiogenesis in the liver and resulted in a loss of the proangiogenic effects of microparticles. Our data identify hepatocyte-derived microparticles as critical signals that contribute to angiogenesis and liver damage in steatohepatitis and suggest a therapeutic target for this condition

Chemical characterization of some substituted hydroxyapatites

Synthetic multi-substituted hydroxyapatite nano powders containing silicon and or carbonate prepared by a wet chemical method. The process parameters are set up to allow the simultaneous substitution of carbonate and silicon ions in the place of phosphorus. The chemical and structural characterizations of the prepared powders are determined with the aid of; XRF, ICP, XRD and FTIR. The results show that, the ion substitution in the crystal lattice of HA caused a change in the unit cell dimensions and affected the degree of crystallization of the produced powders. The apatite formation abilityy of the prepared discs from the synthesized powders is determined by immersing in SBF solution for different periods. The degree of ion release was determined in the obtained solutions. The examined surface of the immersed discs under SEM and analyzed by CDS showed a more dense HA layer than those of un-substituted ones. The HA with the substituted silicon and carbonate ions, showed the highest solubility with greater rate of ion release, compared with carbonate-free powder. All prepared powders took sodium ion from the SBF solution during immersion, which was not recorded before

Ultraviolet and visible reflectance spectra of Phobos and Deimos as measured by the ExoMars-TGO/Nomad-UVIS spectrometer

Spectroscopic measurements are a powerful tool to investigate the surface composition of airless bodies and provide clues of their origin. The composition and origin of Phobos and Deimos are still unknown and are currently widely debated. We present spectroscopic measurements of Phobos and Deimos at ultraviolet and visible wavelengths (250–650 nm) made by the NOMAD-Ultraviolet and Visible Spectrometer (UVIS) on the ExoMars TGO mission. These new spectra cover multiple areas on Phobos and Deimos, and are of generally higher spectral resolution and signal-to-noise than previous spectra, and extend to lower wavelengths than most previous measurements. The UVIS spectra confirm a red-sloped spectrum lacking any strong absorption features; however, we confirm the presence of a previously identified absorption feature near 0.65 μm and tentative absorption near 0.45 μm. The observed Phobos and Deimos spectra are similar to D- and T-type asteroids, adding weight to the captured asteroid hypothesis for the moons' origins. We also find, however, that the UVIS Phobos reflectance spectra of Phobos' red unit is a relatively close match to the olivine-rich, highly shocked Mars meteorite NWA 2737, with a low overall reflectance, a red-sloped spectrum, and lack of olivine-associated absorption bands in the UVIS spectral range. This meteorite, however, exhibits spectral features at longer wavelengths that not observed in the Martian moon spectra, indicating a need for further investigation at longer wavelengths to interpret whether this material could inform our understanding of Phobos' origin

Learning to Selectively Transfer: Reinforced Transfer Learning for Deep Text Matching

Deep text matching approaches have been widely studied for many applications including question answering and information retrieval systems. To deal with a domain that has insufficient labeled data, these approaches can be used in a Transfer Learning (TL) setting to leverage labeled data from a resource-rich source domain. To achieve better performance, source domain data selection is essential in this process to prevent the "negative transfer" problem. However, the emerging deep transfer models do not fit well with most existing data selection methods, because the data selection policy and the transfer learning model are not jointly trained, leading to sub-optimal training efficiency. In this paper, we propose a novel reinforced data selector to select high-quality source domain data to help the TL model. Specifically, the data selector "acts" on the source domain data to find a subset for optimization of the TL model, and the performance of the TL model can provide "rewards" in turn to update the selector. We build the reinforced data selector based on the actor-critic framework and integrate it to a DNN based transfer learning model, resulting in a Reinforced Transfer Learning (RTL) method. We perform a thorough experimental evaluation on two major tasks for text matching, namely, paraphrase identification and natural language inference. Experimental results show the proposed RTL can significantly improve the performance of the TL model. We further investigate different settings of states, rewards, and policy optimization methods to examine the robustness of our method. Last, we conduct a case study on the selected data and find our method is able to select source domain data whose Wasserstein distance is close to the target domain data. This is reasonable and intuitive as such source domain data can provide more transferability power to the model.Comment: Accepted to WSDM 201

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease

A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50–400 nA currents in response to 100 μM L-glutamate. Responses to L-glutamate were concentration-dependent (pEC₅₀ 3.64 ± 0.11). Ibotenate was a partial agonist on IscaGluCl1. We detected no response to 100 μM aspartate, quisqualate, kainate, AMPA or NMDA. Ivermectin at 1 μM activated IscaGluCl1, whereas picrotoxinin (pIC₅₀ 6.20 ± 0.04) and the phenylpyrazole fipronil (pIC₅₀ 6.90 ± 0.04) showed concentration-dependent block of the L-glutamate response. The indole alkaloid okaramine B, isolated from fermentation products of Penicillium simplicissimum (strain AK40) grown on okara pulp, activated IscaGluCl1 in a concentration-dependent manner (pEC₅₀ 5.43 ± 0.43) and may serve as a candidate lead compound for the development of new acaricides