Immunostimulatory activity of polysaccharide-poly(I:C) nanoparticles

Cataloged from PDF version of article.Immunostimulatory properties of mushroom derived polysaccharides (PS) as stand-alone agents were tested. Next. PS were nanocomplexed with polyI:C (pIC) to yield stable nanoparticles around 200 nm in size evidenced by atomic force microscopy and dynamic light scattering analyses. PSs were selectively engaged by cells expressing TLR2 and initiated NF kappa B dependent signaling cascade leading to a Th1-biased cytokine/chemokine secretion in addition to bactericidal nitric oxide (NO) production from macrophages. Moreover, cells treated with nanoparticles led to synergistic IL6, production and upregulation of TNF alpha, MIP3 alpha, IFN gamma and IP10 transcript expression. In mice, PS-Ovalbumin-pIC formulation surpassed anti-OVA IgG responses when compared to either PS-OVA or pIC-OVA mediated immunity. Our results revealed that signal transduction initiated both by TLR2 and TLR3 via co-delivery of pIC by PS in nanoparticle depot delivery system is an effective immunization strategy. The present work implicate that the PS and nucleic acid based nanoparticle approach along with protein antigens can be harnessed to prevent infectious diseases. (C) 2011 Elsevier Ltd. All rights reserve

A time-frequency analysis approach for condition monitoring of a wind turbine gearbox under varying load conditions

This paper deals with the condition monitoring of wind turbine gearboxes under varying operating conditions. Generally, gearbox systems include nonlinearities so a simplified nonlinear gear model is developed, on which the time–frequency analysis method proposed is first applied for the easiest understanding of the challenges faced. The effect of varying loads is examined in the simulations and later on in real wind turbine gearbox experimental data. The Empirical Mode Decomposition (EMD) method is used to decompose the vibration signals into meaningful signal components associated with specific frequency bands of the signal. The mode mixing problem of the EMD is examined in the simulation part and the results in that part of the paper suggest that further research might be of interest in condition monitoring terms. For the amplitude–frequency demodulation of the signal components produced, the Hilbert Transform (HT) is used as a standard method. In addition, the Teager–Kaiser energy operator (TKEO), combined with an energy separation algorithm, is a recent alternative method, the performance of which is tested in the paper too. The results show that the TKEO approach is a promising alternative to the HT, since it can improve the estimation of the instantaneous spectral characteristics of the vibration data under certain conditions

Micro-RNAs Are Related to Epicardial Adipose Tissue in Participants With Atrial Fibrillation: Data From the MiRhythm Study

Introduction: Epicardial adipose tissue (EAT) has been linked to incidence and recurrence of atrial fibrillation (AF), but the underlying mechanisms that mediate this association remain unclear. Circulating microRNAs (miRNAs) contribute to the regulation of gene expression in cardiovascular diseases, including AF. Thus, we sought to test the hypothesis that circulating miRNAs relate to burden of EAT. Methods: We examined the plasma miRNA profiles of 91 participants from the miRhythm study, an ongoing study examining associations between miRNA and AF. We quantified plasma expression of 86 unique miRNAs commonly expressed in cardiomyocytes using quantitative reverse transcriptase polymerase chain reaction (qPCR). From computed tomography, we used validated methods to quantify the EAT area surrounding the left atrium (LA) and indexed it to body surface area (BSA) to calculate indexed LA EAT (iLAEAT). Participants were divided into tertiles of iLAEAT to identify associations with unique miRNAs. We performed logistic regression analyses adjusting for factors associated with AF to examine relations between iLAEAT and miRNA. We performed further bioinformatics analysis of miRNA predicted target genes to identify potential molecular pathways are regulated by the miRNAs. Results: The mean age of the participants was 59 +/- 9, 35% were women, and 97% were Caucasian. Participants in the highest tertile of iLAEAT were more likely to have hypertension, heart failure, and thick posterior walls. In regression analyses, we found that miRNAs 155-5p (p \u3c 0.001) and 302a-3p (p \u3c 0.001) were significantly associated with iLAEAT in patients with AF. The predicted targets of the miRNAs identified were implicated in the regulation of cardiac hypertrophy, adipogenesis, interleukin-8 (IL-8), and nerve growth factor (NGF) signaling. Conclusion: miRNA as well as EAT have previously been linked to AF. Our finding that iLAEAT and miRNAs 155-5p and 302a-3p are associated suggest a possible direct link to between these entities in the development and maintenance of AF. Further research is needed to study causal relationships between these biomarkers

Comprehensive spectroscopic and photometric study of pulsating eclipsing binary star AI Hya

The pulsating eclipsing binaries are remarkable systems that provide an opportunity to probe the stellar interior and to determine the fundamental stellar parameters precisely. Especially the detached eclipsing binary systems with (a) pulsating component(s) are significant objects to understand the nature of the oscillations since the binary effects in these systems are negligible. Recent studies based on space data have shown that the pulsation mechanisms of some oscillating stars are not completely understood. Hence, comprehensive studies of a number of pulsating stars within detached eclipsing binaries are important. In this study, we present a detailed analysis of the pulsating detached eclipsing binary system AI Hya which was studied by two independent groups with different methods. We carried out a spectroscopic survey to estimate the orbital parameters via radial velocity measurements and the atmospheric parameters of each binary component using the composite and/or disentangled spectra. We found that the more luminous component of the system is a massive, cool and chemically normal star while the hotter binary component is a slightly metal-rich object. The fundamental parameters of AI Hya were determined by the analysis of binary variations and subsequently used in the evolutionary modelling. Consequently, we obtained the age of the system as 850 $\pm$ 20 Myr and found that both binary components are situated in the Delta Scuti instability strip. The frequency analysis revealed pulsation frequencies between the 5.5 - 13.0 d$^{-1}$ and we tried to estimate which binary component is the pulsating one. However, it turned out that those frequencies could originate from both binary components.Comment: Accepted for publication in MNRA

The single-sided pulsator CO Camelopardalis

Abstract CO Cam (TIC 160268882) is the second “single-sided pulsator” to be discovered. These are stars where one hemisphere pulsates with a significantly higher amplitude than the other side of the star. CO Cam is a binary star comprised of an Am δ Sct primary star with Teff = 7070 ± 150 K, and a spectroscopically undetected G main-sequence secondary star. The dominant pulsating side of the primary star is centred on the L1 point. We have modelled the spectral energy distribution combined with radial velocities, and independently the TESS light curve combined with radial velocities. Both of these give excellent agreement and robust system parameters for both stars. The δ Sct star is an oblique pulsator with at least four low radial overtone (probably) f modes with the pulsation axis coinciding with the tidal axis of the star, the line of apsides. Preliminary theoretical modelling indicates that the modes must produce much larger flux perturbations near the L1 point, although this is difficult to understand because the pulsating star does not come near to filling its Roche lobe. More detailed models of distorted pulsating stars should be developed. These newly discovered single-sided pulsators offer new opportunities for astrophysical inference from stars that are oblique pulsators in close binary stars

Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. © 2017 Gucluler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Relations between plasma microRNAs, echocardiographic markers of atrial remodeling, and atrial fibrillation: Data from the Framingham Offspring study

BACKGROUND: Circulating microRNAs may reflect or influence pathological cardiac remodeling and contribute to atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to identify candidate plasma microRNAs that are associated with echocardiographic phenotypes of atrial remodeling, and incident and prevalent AF in a community-based cohort. METHODS: We analyzed left atrial function index (LAFI) of 1788 Framingham Offspring 8 participants. We quantified expression of 339 plasma microRNAs. We examined associations between microRNA levels with LAFI and prevalent and incident AF. We constructed pathway analysis of microRNAs\u27 predicted gene targets to identify molecular processes involved in adverse atrial remodeling in AF. RESULTS: The mean age of the participants was 66 +/- 9 years, and 54% were women. Five percent of participants had prevalent AF at the initial examination and 9% (n = 157) developed AF over a median 8.6 years of follow-up (IQR 8.1-9.2 years). Plasma microRNAs were associated with LAFI (N = 73, p \u3c 0.0001). Six of these plasma microRNAs were significantly associated with incident AF, including 4 also associated with prevalent AF (microRNAs 106b, 26a-5p, 484, 20a-5p). These microRNAs are predicted to regulate genes involved in cardiac hypertrophy, inflammation, and myocardial fibrosis. CONCLUSIONS: Circulating microRNAs 106b, 26a-5p, 484, 20a-5p are associated with atrial remodeling and AF