37 research outputs found

    Chronic exposure of gingival fibroblasts to TLR2 or TLR4 agonist inhibits osteoclastogenesis but does not affect osteogenesis

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    Chronic exposure to periodontopathogenic bacteria such as Porphyromonas gingivalis and the products of these bacteria that interact with the cells of the tooth surrounding tissues can ultimately result in periodontitis. This is a disease that is characterized by inflammation-related alveolar bone degradation by the bone-resorbing cells, the osteoclasts. Interactions of bacterial products with Toll-like receptors (TLRs), in particular TLR2 and TLR4, play a significant role in this chronic inflammatory reaction, which possibly affects osteoclastic activity and osteogenic capacity. Little is known about how chronic exposure to specific TLR activators affects these two antagonistic activities. Here, we studied the effect of TLR activation on gingival fibroblasts (GF), cells that are anatomically close to infiltrating bacterial products in the mouth. These were co-cultured with naive osteoclast precursor cells (i.e., monocytes), as part of the peripheral blood mononuclear cells (PBMCs). Activation of GF co-cultures (GF + PBMCs) with TLR2 or TLR4 agonists resulted in a weak reduction of the osteoclastogenic potential of these cultures, predominantly due to TLR2. Interestingly, chronic exposure, especially to TLR2 agonist, resulted in increased release of TNF-α at early time points. This effect, was reversed at later time points, thus suggesting an adaptation to chronic exposure. Monocyte cultures primed with M-CSF + RANKL, led to the formation of bone-resorbing osteoclasts, irrespective of being activated with TLR agonists. Late activation of these co-cultures with TLR2 and with TLR4 agonists led to a slight decrease in bone resorption. Activation of GF with TLR2 and TLR4 agonists did not affect the osteogenic capacity of the GF cells. In conclusion, chronic exposure leads to diverse reactions; inhibitory with naive osteoclast precursors, not effecting already formed (pre-)osteoclasts. We suggest that early encounter of naive monocytes with TLR agonists may result in differentiation toward the macrophage lineage, desirable for clearing bacterial products. Once (pre-)osteoclasts are formed, these cells may be relatively insensitive for direct TLR stimulation. Possibly, TLR activation of periodontal cells indirectly stimulates osteoclasts, by secreting osteoclastogenesis stimulating inflammatory cytokines

    Mapping of DNA methylationsensitive cellular processes in gingival and periodontal ligament fibroblasts in the context of periodontal tissue homeostasis

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    Interactions between gingival fibroblasts (GFs) and oral pathogens contribute to the chronicity of inflammation in periodontitis. Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis, and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against epithelial barrier disruption and bone resorption. To assess the impact of DNMT inhibition on GFs, cells were cultured with decitabine (5-aza-2’-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. We observed several potentially detrimental effects of DAC on GF biological functions. First, extended treatment with DAC reduced GF proliferation and induced necrotic cell death. Second, DAC amplified Porphyromonas gingivalis- and cytokine-induced expression and secretion of the chemokine CCL20 and several matrix metalloproteinases (MMPs), including MMP1, MMP9, and MMP13. Similar pro-inflammatory effects of DAC were observed in periodontal ligament fibroblasts. Third, DAC upregulated intercellular adhesion molecule-1 (ICAM-1), which was associated with increased P. gingivalis adherence to GFs and may contribute to bacterial dissemination. Finally, analysis of DAC-induced genes identified by RNA sequencing revealed increased expression of CCL20, CCL5, CCL8, CCL13, TNF, IL1A, IL18, IL33, and CSF3, and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Our observations demonstrate that studies of DNMT inhibitors provide important insights into the role of DNA methylation in cells involved in periodontitis pathogenesis. However, the therapeutic potential of hypomethylating agents in periodontal disease may be limited due to their cytotoxic effects on fibroblast populations and stimulation of pro-inflammatory pathways.</p

    Polaritonic molecular clock for all-optical ultrafast imaging of wavepacket dynamics without probe pulses

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    Conventional approaches to probing ultrafast molecular dynamics rely on the use of synchronized laser pulses with a well-defined time delay. Typically, a pump pulse excites a molecular wavepacket. A subsequent probe pulse can then dissociate or ionize the molecule, and measurement of the molecular fragments provides information about where the wavepacket was for each time delay. Here, we propose to exploit the ultrafast nuclear-position-dependent emission obtained due to large light–matter coupling in plasmonic nanocavities to image wavepacket dynamics using only a single pump pulse. We show that the time-resolved emission from the cavity provides information about when the wavepacket passes a given region in nuclear configuration space. This approach can image both cavity-modified dynamics on polaritonic (hybrid light–matter) potentials in the strong light–matter coupling regime and bare-molecule dynamics in the intermediate coupling regime of large Purcell enhancements, and provides a route towards ultrafast molecular spectroscopy with plasmonic nanocavitiesThis work has been funded by the European Research Council grant ERC-2016-STG-714870 and the Spanish Ministry for Science, Innovation, and Universities—AEI grants RTI2018-099737-B-I00, PCI2018-093145 (through the QuantERA program of the European Commission), and CEX2018-000805-M (through the María de Maeztu program for Units of Excellence in R&D

    Testing for a difference between conditional variance functions of nonlinear time series

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    In this report, the problem of testing for a difference between conditional variance fnuctions (or volatilites) of two independent nonlinear time series is investigated by means of an extensive simulation study. Empirical results on the properties of the test proposed confirm the test's validity, at least for some types of heteroscedasticity as contrasted with homnoscedastic erroos as well as for some types of differences in heteooscedasticity. Moreover, interesting properties of several estimators of conditional mean, variance and fourth moment functions are empirically found too

    Efficiency of operation for the Military Economic Unit (MEU)

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    W strukturze zapewnienia Siłom Zbrojnym RP zdolności do działań istotne znaczenie posiadają specjalistyczne jednostki logistyczne - wojskowe oddziały gospodarcze (WOG), których zadaniem jest odciążanie jednostek przeznaczanych do realizacji zadań szkoleniowych/bojowych w zakresie zabezpieczenia logistycznego. Realizacja trudnych zadań merytorycznych wymaga profesjonalizmu kadry WOG i powinna być oceniana pod względem efektywności funkcjonowania, poprzez analizę uzyskiwanych wyników, również w aspekcie ekonomicznym. W pracy przedstawiono zastosowanie funkcji rentowności zarządczej jako formy oceny działalności WOG obejmującej zróżnicowane uwarunkowania realizacyjne w zdeterminowanych okresach czasowych.Specialised logistic entities hereby named as Military Economic Units (MEU) have a significant meaning in the structure providing operational capabilities for the Polish Armed Forces through relieving the military units involved in drilling/combat operations in the logistic tasks. The performance of difficult objective tasks demands a presence of professional staff in the MEU and its efficiency of operation has to be evaluated by an analysis of received results, also in a financial aspect. The paper describes an application of a managerial profitability function as a form of assessment for the MEU activities which includes different conditions for execution in determined time frames

    Specific heat and magnetocaloric effect in Ho-Er-Co solid solutions

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    Specific heat measurements have been performed on polycrystalline HoCo2, ErCo2 and their solid solutions Ho1−x Er x Co2 (0.1≤x≤0.5). These compounds were synthesized using high-purity rare-earth metals and cobalt. X-ray diffraction patterns taken at room temperature reveal that all compounds have the C15 cubic Laves phase structure. Heat capacity measurements have been performed in the temperature range of 2–300 K without magnetic field and in a magnetic field of 1 and 2 T. The magnetocaloric effect has been estimated in terms of isothermal magnetic entropy change for all solid solutions in magnetic fields up to 2 T. The effect of increasing Er amount in Ho1−x Er x Co2 on the magnetic and magnetocaloric properties will be discussed

    Specific Heat of the Tb1xLaxNi2Tb_{1-x}La_xNi_2 Solid Solutions

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    Specific heat measurements have been performed on the polycrystalline TbNi2,LaNi2TbNi_2, LaNi_2 and their solid solutions Tb1xLaxNi2Tb_{1-x}La_xNi_2 (x=0.2, 0.3). The Debye temperatures, phonon and conduction electron contributions as well as the magnetic part of the heat capacity were determined and discussed. The magnetocaloric effect was estimated from measurements performed in a magnetic field of 0.42 T for TbNi2,TbNi_2, Tb0.8La0.2Ni2Tb_{0.8}La_{0.2}Ni_2 and Tb0.7La0.3Ni2Tb_{0.7}La_{0.3}Ni_2
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