Role of IL-33 in inflammation and disease

Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP), both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro-or anti-inflammatory depending on the disease and the model. In this review the role of IL-33 in the inflammation of several disease pathologies will be discussed, with particular emphasis on recent advances

Analyzing Songs Used for Lyric Analysis With Mental Health Consumers Using Linguistic Inquiry and Word Count (LIWC) Software

Lyric analysis is one of the most commonly used music therapy interventions with the mental health population, yet there is a gap in the research literature regarding song selection. The primary purpose of this study was to determine distinguishing linguistic characteristics of song lyrics most commonly used for lyric analysis with mental health consumers, as measured by LIWC2015 software. A secondary purpose was to provide an updated song list resource for music therapists and music therapy students working with the mental health population. The researcher emailed a survey to 6,757 board-certified music therapists, 316 of whom completed the survey. Respondents contributed 700 different songs that they deemed most effective for lyric analysis with mental health consumers. The researcher used the LIWC2015 software to analyze the 48 songs that were listed by five or more music therapists. Song lyrics contained linguistic indicators of self-focused attention, present-focused attention, poor social relationships, and high cognitive processing. Lyrics were written in an informal, personal, and authentic style. Some lyrics were more emotionally positive, while others were more emotionally negative. While results must be interpreted with caution, it may be helpful to consider linguistic elements when choosing songs for lyric analysis with mental health consumers

The Fundamental Plane of Black Hole Accretion and its Use as a Black Hole-Mass Estimator

We present an analysis of the fundamental plane of black hole accretion, an empirical correlation of the mass of a black hole ($M$), its 5 GHz radio continuum luminosity ($\nu L_{\nu}$), and its 2-10 keV X-ray power-law continuum luminosity ($L_X$). We compile a sample of black holes with primary, direct black hole-mass measurements that also have sensitive, high-spatial-resolution radio and X-ray data. Taking into account a number of systematic sources of uncertainty and their correlations with the measurements, we use Markov chain Monte Carlo methods to fit a mass-predictor function of the form $\log(M/10^{8}\,M_{\scriptscriptstyle \odot}) = \mu_0 + \xi_{\mu R} \log(L_R / 10^{38}\,\mathrm{erg\,s^{-1}}) + \xi_{\mu X} \log(L_X / 10^{40}\,\mathrm{erg\,s^{-1}})$. Our best-fit results are $\mu_0 = 0.55 \pm 0.22$, $\xi_{\mu R} = 1.09 \pm 0.10$, and $\xi_{\mu X} = -0.59^{+0.16}_{-0.15}$ with the natural logarithm of the Gaussian intrinsic scatter in the log-mass direction $\ln\epsilon_\mu = -0.04^{+0.14}_{-0.13}$. This result is a significant improvement over our earlier mass scaling result because of the increase in active galactic nuclei sample size (from 18 to 30), improvement in our X-ray binary sample selection, better identification of Seyferts, and improvements in our analysis that takes into account systematic uncertainties and correlated uncertainties. Because of these significant improvements, we are able to consider potential influences on our sample by including all sources with compact radio and X-ray emission but ultimately conclude that the fundamental plane can empirically describe all such sources. We end with advice for how to use this as a tool for estimating black hole masses.Comment: ApJ Accepted. Online interactive version of Figure 7 available at http://kayhan.astro.lsa.umich.edu/supplementary_material/fp

What is on Tap? The Role of Spin in Compact Objects and Relativistic Jets

We examine the role of spin in launching jets from compact objects across the mass scale. Our work includes a total of 37 Seyferts, 11 stellar-mass black holes, and 13 neutron stars. We find that when the Seyfert reflection lines are modeled with Gaussian line features (a crude proxy for inner disk radius and therefore spin), only a slight inverse correlation is found between the Doppler-corrected radio luminosity at 5 GHz (a proxy for jet power) and line width. When the Seyfert reflection features are fit with relativistically-blurred disk reflection models that measure spin, there is a tentative positive correlation between the Doppler-corrected radio luminosity and the spin measurement. Further, when we include stellar-mass black holes in the sample, to examine the effects across the mass scale, we find a slightly stronger correlation with radio luminosity per unit mass and spin, at a marginal significance (2.3 sigma confidence level). Finally, when we include neutron stars, in order to probe lower spin values, we find a positive correlation (3.3 sigma confidence level) between radio luminosity per unit mass and spin. Although tentative, these results suggest that spin may have a role in determining the jet luminosity. In addition, we find a slightly more significant correlation (4.4 sigma confidence level) between radio luminosity per Bolometric luminosity and spin, using our entire sample of black holes and neutrons stars. Again, although tentative, these relations point to the possibility that the mass accretion rate, i.e. Bolometric luminosity, is also important in determining the jet luminosity, in addition to spin. Our analysis suggests that mass accretion rate and disk or coronal magnetic field strength may be the "throttle" in these compact systems, to which the Eddington limit and spin may set the maximum jet luminosity that can be achieved.Comment: 14 pages, 13 Figures, ApJ Accepte

miR-34a-/- mice are susceptible to diet-induced obesity

Objective: MicroRNA (miR)−34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated. Methods: Wild-type (WT) and miR-34a−/− mice were fed chow or high-fat diet (HFD) for 24 weeks. WT and miR-34a−/− bone marrow-derived macrophages were cultured in vitro with macrophage colony-stimulating factor (M-CSF). Brown and white preadipocytes were cultured from the stromal vascular fraction (SVF) of intrascapular brown and epididymal white adipose tissue (eWAT), with rosiglitazone. Results: HFD-fed miR-34a−/− mice were significantly heavier with a greater increase in eWAT weight than WT. miR-34a−/− eWAT had a smaller adipocyte area, which significantly increased with HFD. miR-34a−/− eWAT showed basal increases in Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a−/− intrascapular brown adipose tissue had basal reductions in c/ebpα and c/ebpβ, with in vitro miR-34a−/− white adipocytes showing increased lipid content. An F4/80high macrophage population was present in HFD miR-34a−/− eWAT, with increased IL-10 transcripts and serum IL-5 protein. Finally, miR-34a−/− bone marrow-derived macrophages showed an ablated CXCL1 response to tumor necrosis factor-α. Conclusions: These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways

Distinct phosphorylation clusters determines the signalling outcome of the free fatty acid receptor FFA4/GPR120

It is established that long-chain free fatty acids including ω-3 fatty acids mediate an array of biological responses through members of the free fatty acid receptor family, which includes FFA4. However, the signalling mechanisms and modes of regulation of this receptor class remain unclear. Here we employ mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C terminal tail, designated cluster 1 (Thr347, Thr349 and Ser350) and cluster 2 (Ser357 and Ser361). Mutation of these phospho-acceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to ERK1/2 activation. Rather an inhibitor of Gq/11 proteins completely prevented receptor signalling to ERK1/2. In contrast, the recruitment of arrestin 3, receptor internalization and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signalling was extended further by selective mutations of the phospho-acceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phospho-acceptor sites within cluster 1 had no effect on receptor internalization and a less extensive effect on arrestin 3 recruitment, but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signalling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signalling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C-terminus of the receptor