16 research outputs found
Polarization and spectral energy distribution in OJ 287 during the 2016/17 outbursts
We report optical photometric and polarimetric observations of the blazar OJ 287 gathered during 2016/17. The high level of activity, noticed after the General Relativity Centenary flare, is argued to be part of the follow-up flares that exhibited high levels of polarization and originated in the primary black hole jet. We propose that the follow-up flares were induced as a result of accretion disk perturbations, travelling from the site of impact towards the primary SMBH. The timings inferred from our observations allowed us to estimate the propagation speed of these perturbations. Additionally, we make predictions for the future brightness of OJ 287. © 2017 by the authors
GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis
Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE
Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+T cells in aged rats
Background: Aging influences immune response and susceptibility to EAE in a strain specific manner. The study was designed to examine influence of aging on EAE induction in Albino Oxford (AO) rats. Results: Differently from 3-month-old (young) rats, which were resistant to EAE induction, the majority of aged (24-26-month-old) rats developed mild chronic form of EAE. On 16th day post-immunization, when in aged rats the neurological deficit reached plateau, more mononuclear cells, including CD4+ T lymphocytes was retrieved from spinal cord of aged than young rats. The frequencies of IL-17+ and GM-CSF+ cells within spinal cord infiltrating CD4+ lymphocytes were greater in aged rats. To their increased frequency contributed the expansion of GM-CSF + IL-17 + IFN-gamma+ cells, which are highly pathogenic in mice. The expression of the cytokines (IL-1 beta and IL-23/p19) driving GM-CSF + IL-17 + IFN-gamma + cell differentiation in mice was also augmented in aged rat spinal cord mononuclear cells. Additionally, in aged rat spinal cord the expansion of GM-CSF + IL-17-IFN-gamma- CD4+ T lymphocytes was found. Consistently, the expression of mRNAs for IL-3, the cytokine exhibiting the same expression pattern as GM-CSF, and IL-7, the cytokine driving differentiation of GM-CSF + IL-17-IFN-gamma- CD4 + lymphocytes in mice, was upregulated in aged rat spinal cord mononuclear cells, and the tissue, respectively. This was in accordance with the enhanced generation of the brain antigen-specific GM-CSF+ CD4+ lymphocytes in aged rat draining lymph nodes, as suggested by (i) the higher frequency of GM-CSF+ cells (reflecting the expansion of IL-17-IFN-gamma- cells) within their CD4+ lymphocytes and (ii) the upregulated GM-CSF and IL-3 mRNA expression in fresh CD4+ lymphocytes and MBP-stimulated draining lymph node cells and IL-7 mRNA in lymph node tissue from aged rats. In agreement with the upregulated GM-CSF expression in aged rats, strikingly more CD11b + CD45(int) (activated microglia) and CD45(hi) (mainly proinflammatory dendritic cells and macrophages) cells was retrieved from aged than young rat spinal cord. Besides, expression of mRNA for SOCS1, a negative regulator of proinflammatory cytokine expression in innate immunity cells, was downregulated in aged rat spinal cord mononuclear cells. Conclusions: The study revealed that aging may overcome genetic resistance to EAE, and indicated the cellular and molecular mechanisms contributing to this phenomenon in AO rats
Diminished macrophage apoptosis and reactive oxygen species generation after phorbol ester stimulation in Crohn's disease.
BACKGROUND: Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. METHODOLOGY/PRINCIPAL FINDINGS: Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. CONCLUSION: These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD
Polarization and spectral energy distribution in OJ 287 during the 2016/17 outbursts
© 2017 by the authors. We report optical photometric and polarimetric observations of the blazar OJ 287 gathered during 2016/17. The high level of activity, noticed after the General Relativity Centenary flare, is argued to be part of the follow-up flares that exhibited high levels of polarization and originated in the primary black hole jet. We propose that the follow-up flares were induced as a result of accretion disk perturbations, travelling from the site of impact towards the primary SMBH. The timings inferred from our observations allowed us to estimate the propagation speed of these perturbations. Additionally, we make predictions for the future brightness of OJ 287
Stochastic Modeling of Multiwavelength Variability of the Classical BL Lac Object OJ287 on Timescales Ranging from Decades to Hours
We present the results of our power spectral density analysis for the BL Lac object OJ 287, utilizing the Fermi-LAT survey at high-energy.-rays, Swift-XRT in X-rays, several ground-based telescopes and the Kepler satellite in the optical, and radio telescopes at GHz frequencies. The light curves are modeled in terms of continuous-time autoregressive moving average (CARMA) processes. Owing to the inclusion of the Kepler data, we were able to construct for the first time the optical variability power spectrum of a blazar without any gaps across similar to 6 dex in temporal frequencies. Our analysis reveals that the radio power spectra are of a colored-noise type on timescales ranging from tens of years down to months, with no evidence for breaks or other spectral features. The overall optical power spectrum is also consistent with a colored noise on the variability timescales ranging from 117 years down to hours, with no hints of any quasi-periodic oscillations. The X-ray power spectrum resembles the radio and optical power spectra on the analogous timescales ranging from tens of years down to months. Finally, the.-ray power spectrum is noticeably different from the radio, optical, and X-ray power spectra of the source: we have detected a characteristic relaxation timescale in the Fermi-LAT data, corresponding to similar to 150 days, such that on timescales longer than this, the power spectrum is consistent with uncorrelated (white) noise, while on shorter variability timescales there is correlated (colored) noise
“Cationic” Suzuki–Miyaura Coupling with Acutely Base-Sensitive Boronic Acids
Fast,
base-promoted protodeboronation of polyfluoroaryl and heteroaryl
boronic acids complicates their use in Suzuki–Miyaura coupling
(SMC) because a base is generally required for catalysis. We report
a “cationic” SMC method using a PAd<sub>3</sub>-Pd catalyst
that proceeds at rt in the absence of a base or metal mediator. A
wide range of sensitive boronic acids, particularly polyfluoroaryl
substrates that are poorly compatible with classic SMC conditions,
undergo clean coupling. Stoichiometric experiments implicate the intermediacy
of organopalladium cations, which supports a long-postulated cationic
pathway for transmetalation in SMC
Polarization and spectral energy distribution in OJ 287 during the 2016/17 outbursts
© 2017 by the authors. We report optical photometric and polarimetric observations of the blazar OJ 287 gathered during 2016/17. The high level of activity, noticed after the General Relativity Centenary flare, is argued to be part of the follow-up flares that exhibited high levels of polarization and originated in the primary black hole jet. We propose that the follow-up flares were induced as a result of accretion disk perturbations, travelling from the site of impact towards the primary SMBH. The timings inferred from our observations allowed us to estimate the propagation speed of these perturbations. Additionally, we make predictions for the future brightness of OJ 287
Polarization and spectral energy distribution in OJ 287 during the 2016/17 outbursts
We report optical photometric and polarimetric observations of the blazar OJ 287 gathered during 2016/17. The high level of activity, noticed after the General Relativity Centenary flare, is argued to be part of the follow-up flares that exhibited high levels of polarization and originated in the primary black hole jet. We propose that the follow-up flares were induced as a result of accretion disk perturbations, travelling from the site of impact towards the primary SMBH. The timings inferred from our observations allowed us to estimate the propagation speed of these perturbations. Additionally, we make predictions for the future brightness of OJ 287. © 2017 by the authors
Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains
Altered functions of macrophages with aging contribute to impairment of both innate and adaptive immunity in the elderly. The present study aimed to examine strain specificity of age-related changes in the phenotypic and functional characteristics of macrophages from DA and AO rats, which differ in average life span. Resident peritoneal macrophages from young (10-12 weeks old) and aged (98-104 weeks old) rats were tested for: (a) the surface expression of TLR4 and CD14; (b) the basal and LPS-induced production of TNF-alpha and IL-10; and (c) the basal and LPS-induced activity of iNOS and arginase, by measuring the levels of NO and urea, respectively, in the culture supernatants. Aging elevated TLR4 macrophage surface density in rats of both strains. Conversely, the age-related decrease in the surface density of CD14 co-receptor was detected only on macrophages from aged DA rats. Accordingly, with aging in DA rats, contrary to AO rats, upon LPS-stimulation both TNF-alpha and IL-10 levels decreased in culture supernatants. However, in rats of both strains TNF-alpha stimulation index (LPS-induced over basal production) remained stable with aging, but it was significantly greater in AO rats. Furthermore, with aging, IL-10 stimulation index decreased and increased in DA and AO rats, respectively. Age-related shift in urea stimulation index complied with the changes of IL-10 stimulation index during aging. In conclusion, the study suggests that the preserved ability of macrophages from aged AO rats to synthesize not only proinflammatory TNF-alpha, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats