The secreted protein, YKL-40, has been proposed as a biomarker of a variety of human diseases characterized by ongoing inflammation, including chronic neurologic pathologies such as multiple ...sclerosis and Alzheimer's disease. However, inflammatory mediators and the molecular mechanism responsible for enhanced expression of YKL-40 remained elusive. Using several mouse models of inflammation, we now show that YKL-40 expression correlated with increased expression of both IL-1 and IL-6. Furthermore, IL-1 together with IL-6 or the IL-6 family cytokine, oncostatin M, synergistically upregulated YKL-40 expression in both primary human and mouse astrocytes in vitro. The robust cytokine-driven expression of YKL-40 in astrocytes required both STAT3 and NF-κB binding elements of the YKL-40 promoter. In addition, YKL-40 expression was enhanced by constitutively active STAT3 and inhibited by dominant-negative IκBα. Surprisingly, cytokine-driven expression of YKL-40 in astrocytes was independent of the p65 subunit of NF-κB and instead required subunits RelB and p50. Mechanistically, we show that IL-1-induced RelB/p50 complex formation was further promoted by oncostatin M and that these complexes directly bound to the YKL-40 promoter. Moreover, we found that expression of RelB was strongly upregulated during inflammation in vivo and by IL-1 in astrocytes in vitro. We propose that IL-1 and the IL-6 family of cytokines regulate YKL-40 expression during sterile inflammation via both STAT3 and RelB/p50 complexes. These results suggest that IL-1 may regulate the expression of specific anti-inflammatory genes in nonlymphoid tissues via the canonical activation of the RelB/p50 complexes.
Summary
This study investigated the ecological distribution of zoonotic bacterial pathogen, Campylobacter, in mixed crop–livestock (MCL) farms compared to conventional farms and their products at ...pre‐ and post‐harvest levels. A total of 222 Campylobacter isolates were identified. At pre‐harvest level, a total of 1287 samples from seven MCL farms, four conventional poultry farms, four organic produce‐only and five conventional produce‐only farms from Maryland and the DC metropolitan area were analysed from 2012 to 2014. Campylobacter was detected in 11.16% and 3.6% of MCL and conventional farm samples, respectively, but none from produce‐only farm samples. Tetracycline resistance was observed in 51.02% of MCL farm isolates but none among conventional farm isolates. For post‐harvest analysis, a total of 1281 food products from seven farmers markets, three organic retail supermarkets and three conventional retail supermarkets were collected from the same area. Campylobacter was isolated in 87.5%, 71.43% and 33.33% of whole chicken carcasses in farmers markets, organic and conventional retail supermarkets, respectively. No Campylobacter was detected in post‐harvest produce samples due in part to the inability of Campylobacter to survive in absence of sufficient water activity. Overall, this study reveals public health concerns regarding the MCL farm environment and their products that are sold in retail and farmers markets.
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). It is firmly established that overactivation of the p65 (RelA) nuclear factor kappa B (NF-κB) ...transcription factor upregulates expression of inflammatory mediators in both immune and non-immune resident CNS cells and promotes inflammation during MS. In contrast to p65, NF-κB family member RelB regulates immune cell development and can limit inflammation. Although RelB expression is induced during inflammation in the CNS, its role in MS remains unknown.
To examine the role of RelB in non-immune CNS cells, we generated mice with RelB specifically deleted in astrocytes (RelB
), oligodendrocytes (RelB
), or neural progenitor-derived cells (RelB
). We used experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS, to assess the effect of RelB deletion on disease outcomes and performed analysis on the histological, cellular, and molecular level.
Despite being a negative regulator of inflammation, conditional knockout of RelB in non-immune resident CNS cells surprisingly decreased the severity of EAE. This protective effect was recapitulated by conditional deletion of RelB in oligodendrocytes but not astrocytes. Deletion of RelB in oligodendrocytes reduced disease severity, promoted survival of mature oligodendrocytes, and correlated with increased activation of p65 NF-κB.
These findings suggest that RelB fine tunes inflammation and cell death/survival during EAE. Importantly, our data points out the detrimental role RelB plays in controlling survival of mature oligodendrocytes, which could be explored as a viable option to treat MS in the future.
We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,μ), using the full data sample of 772×10^{6} BBover ¯ pairs recorded by the Belle detector at the KEKB ...asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.
Inverted papillomas are rare benign neoplasms that typically originate in the sinonasal area of middle-aged men. We report the first case of a supraglottic inverted papilloma presenting with stridor.
The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively ...straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6<Q^{2}<2.9 GeV^{2}, where existing measurements give inconsistent results. The precision and Q^{2} range of these data allow for a better understanding of the current world's data and suggest a path toward further improvement of our overall understanding of the neutron's magnetic form factor.
We report here on the generation of simulated defects on sintered uranium dioxide fuel pellets by taking advantage of the underwater laser ablation procedure and their subsequent characterization. ...This work, we believe, can play a role towards the validation of the performance of fuel pellet inspection machines. A repetitive fiber laser, capable of delivering pulses of nanosecond duration, in conjunction with a galvo-scanner served as the machining tool in the experiment. The study of the dependence of mass ablation rate on laser fluence, water column height, repetition rate, and beam scanning speed formed the bulk of this work. A water column of height ∼3 mm above the pellet surface in combination with a laser fluence of lying within 6–7 J/cm2 yielded the maximum ablation rate. The generated defects were analyzed using optical and electron microscopy. Clean defects, e.g. longitudinal cracks, circumferential cracks, pits, and end caps of different sizes and depths were created on the pellet surface by varying the laser parameters, beam travel trajectory, and beam scanning parameters. The mechanical pressure arising out of shock wave generated as a result of the confinement of the laser-produced plasma and the collapse of cavitation bubbles together with the microfluid jet formed due to the implosion of the bubbles pushed the molten ablated products from the interaction zone thereby facilitating the generation of cleaned machined surfaces. An insight into the physical processes’ operative in the underwater laser machining process has been offered, albeit qualitatively.
•Simulated defects were generated on sintered UO2 pellets using a pulsed fiber laser.•The defects, e.g. pits, cracks, missing surface area were formed by laser ablation.•The dimension of the fabricated defects can be controlled.•Underwater ablation resulted in cleaner defects without any bulging near the edge.•Defective pellets can be utilized for authentication of pellet inspection machines.
Abstract
Metrology of electron wavepackets is often conducted with the technique of photoelectron interferometry. However, the ultrashort light pulses employed in this method place a limit on the ...energy resolution. Here, weadvance ultrafast photoelectron interferometry access both high temporal and spectral resolution. The key to our approach lies in stimulating Raman interferences with a probe pulse and while monitoring the modification of the autoionizing electron yield in a separate delayed detection step. As a proof of the principle, we demonstrated this technique to obtain the components of an autoionizing
nf′
wavepacket between the spin-orbit split ionization thresholds in argon. We extracted the amplitudes and phases from the interferogram and compared the experimental results with second-order perturbation theory calculations. This high resolution probing and metrology of electron dynamics opens the path for study of molecular wavepackets.
The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics ...and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities
that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities
map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades
. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.
Immune activation, neuroinflammation, and cell death are the hallmarks of multiple sclerosis (MS), which is an autoimmune demyelinating disease of the central nervous system (CNS). It is ...well-documented that the cellular inhibitor of apoptosis 2 (cIAP2) is induced by inflammatory stimuli and regulates adaptive and innate immune responses, cell death, and the production of inflammatory mediators. However, the impact of cIAP2 on neuroinflammation associated with MS and disease severity remains unknown.
We used experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of MS, to assess the effect of cIAP2 deletion on disease outcomes. We performed a detailed analysis on the histological, cellular, and molecular levels. We generated and examined bone-marrow chimeras to identify the cIAP2-deficient cells that are critical to the disease outcomes.
cIAP2
mice exhibited increased EAE severity, increased CD4
T cell infiltration, enhanced proinflammatory cytokine/chemokine expression, and augmented demyelination. This phenotype was driven by cIAP2-deficient non-hematopoietic cells. cIAP2 protected oligodendrocytes from cell death during EAE by limiting proliferation and activation of brain microglia. This protective role was likely exerted by cIAP2-mediated inhibition of the non-canonical NLRP3/caspase-8-dependent myeloid cell activation during EAE.
Our findings suggest that cIAP2 is needed to modulate neuroinflammation, cell death, and survival during EAE. Significantly, our data demonstrate the critical role of cIAP2 in limiting the activation of microglia during EAE, which could be explored for developing MS therapeutics in the future.
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