Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis

Background. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC). Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFα than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects

Nearest-Neighbor-Atom Core-Hole Transfer in Isolated Molecules

A new phenomenon sensitive only to next-door-neighbor atoms in isolated molecules is demonstrated using angle-resolved photoemission of site-selective core electrons. Evidence for this interatomic core-to-core electron interaction is observable only by measuring nondipolar angular distributions of photoelectrons. In essence, the phenomenon acts as a very fine atomic-scale sensor of nearest-neighbor elemental identity

Altered coronary artery function, arteriogenesis and endothelial YAP signaling in postnatal hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a cardiovascular genetic disease caused largely by sarcomere protein mutations. Gaps in our understanding exist as to how maladaptive sarcomeric biophysical signals are transduced to intra- and extracellular compartments leading to HCM progression. To investigate early HCM progression, we focused on the onset of myofilament dysfunction during neonatal development and examined cardiac dynamics, coronary vascular structure and function, and mechano-transduction signaling in mice harboring a thin-filament HCM mutation.Methods: We studied postnatal days 7–28 (P7–P28) in transgenic (TG) TG-cTnT-R92Q and non-transgenic (NTG) mice using skinned fiber mechanics, echocardiography, biochemistry, histology, and immunohistochemistry.Results: At P7, skinned myofiber bundles exhibited an increased Ca2+-sensitivity (pCa50 TG: 5.97 ± 0.04, NTG: 5.84 ± 0.01) resulting from cTnT-R92Q expression on a background of slow skeletal (fetal) troponin I and α/β myosin heavy chain isoform expression. Despite the transition to adult isoform expressions between P7–P14, the increased Ca2+- sensitivity persisted through P28 with no apparent differences in gross morphology among TG and NTG hearts. At P7 significant diastolic dysfunction was accompanied by coronary flow perturbation (mean diastolic velocity, TG: 222.5 ± 18.81 mm/s, NTG: 338.7 ± 28.07 mm/s) along with localized fibrosis (TG: 4.36% ± 0.44%, NTG: 2.53% ± 0.47%). Increased phosphorylation of phospholamban (PLN) was also evident indicating abnormalities in Ca2+ homeostasis. By P14 there was a decline in arteriolar cross-sectional area along with an expansion of fibrosis (TG: 9.72% ± 0.73%, NTG: 2.72% ± 0.2%). In comparing mechano-transduction signaling in the coronary arteries, we uncovered an increase in endothelial YAP expression with a decrease in its nuclear to cytosolic ratio at P14 in TG hearts, which was reversed by P28.Conclusion: We conclude that those early mechanisms that presage hypertrophic remodeling in HCM include defective biophysical signals within the sarcomere that drive diastolic dysfunction, impacting coronary flow dynamics, defective arteriogenesis and fibrosis. Changes in mechano-transduction signaling between the different cellular compartments contribute to the pathogenesis of HCM

Study of ultrathin Pt/Co/Pt trilayers modified by nanosecond XUV pulses from laser-driven plasma source

We have studied the structural mechanisms responsible for the magnetic reorientation between in-plane and out-of-plane magnetization in the (25 nm Pt)/(3 and 10 nm Co)/(3 nm Pt) trilayer systems irradiated with nanosecond XUV pulses generated with laser-driven gas-puff target plasma source of a narrow continuous spectrum peaked at wavelength of 11 nm. The thickness of individual layers, their density, chemical composition and irradiation-induced lateral strain were deduced from symmetric and asymmetric X-ray diffraction (XRD) patterns, grazing-incidence X-ray reflectometry (GIXR), grazing incidence X-ray fluorescence (GIXRF), extended X-ray absorption fine structure (EXAFS) and transmission electron microscopy (TEM) measurements. In the as grown samples we found, that the Pt buffer layers are relaxed and that the layer interfaces are sharp. As a result of a quasi-uniform irradiation of the samples, the XRD, EXAFS, GIXR and GIXRF data reveal the formation of two distinct layers composed of Pt1-xCox alloys with different Co concentrations, dependent on the thickness of the as grown magnetic Co film but with similar ∼1% lateral tensile residual strain. For smaller exposure dose (lower number of accumulated pulses) only partial interdiffusion at the interfaces takes place with the formation of a tri-layer composed of Co-Pt alloy sandwiched between thinned Pt layers, as revealed by TEM. The structural modifications are accompanied by magnetization changes, evidenced by means of magneto-optical microscopy. The difference in magnetic properties of the irradiated samples can be related to their modification in Pt1-xCox alloy composition, as the other parameters (lateral strain and alloy thickness) remain almost unchanged. The out-of-plane magnetization observed for the sample with initially 3 nm Co layer can be due to a significant reduction of demagnetization factor resulting from a lower Co concentration

Doped nanoparticles for optoelectronics applications

Nanoparticles of wide band gap materials doped with transition metal ions or rare earth ions are intensively studied for their possible applications in a new generation of light sources for an overhead illumination. In this work we discuss mechanisms of emission enhancement in nanoparticles doped with rare earth or/and transition metal ions. Arguments are presented that phosphors of nanosize may emit light more efficiently and thus be applied in practical optoelectronic devices

Investigating the Effect of Emoji in Opinion Classification of Uzbek Movie Review Comments

Opinion mining on social media posts has become more and more popular. Users often express their opinion on a topic not only with words but they also use image symbols such as emoticons and emoji. In this paper, we investigate the effect of emoji-based features in opinion classification of Uzbek texts, and more specifically movie review comments from YouTube. Several classification algorithms are tested, and feature ranking is performed to evaluate the discriminative ability of the emoji-based features.Comment: 10 pages, 1 figure, 3 table