Supplementary Material for: Effects of Obesity on Perivascular Adipose Tissue Vasorelaxant Function: Nitric Oxide, Inflammation and Elevated Systemic Blood Pressure

<b><i>Introduction:</i></b> Perivascular adipose tissue (PVAT) surrounds most vessels in the human body. Healthy PVAT has a vasorelaxant effect which is not observed in obesity. We assessed the contribution of nitric oxide (NO), inflammation and endothelium to obesity-induced PVAT damage. <b><i>Methods:</i></b> Rats were fed a high-fat diet or normal chow. PVAT function was assessed using wire myography. Skeletonised and PVAT-intact mesenteric vessels were prepared with and without endothelium. Vessels were incubated with L-NNA or superoxide dismutase (SOD) and catalase. Gluteal fat biopsies were performed on 10 obese and 10 control individuals, and adipose tissue was assessed using proteomic analysis. <b><i>Results:</i></b> In the animals, there were significant correlations between weight and blood pressure (BP; r = 0.5, p = 0.02), weight and PVAT function (r = 0.51, p = 0.02), and PVAT function and BP (r = 0.53, p = 0.01). PVAT-intact vessel segments from healthy animals constricted significantly less than segments from obese animals (p < 0.05). In a healthy state, there was preservation of the PVAT vasorelaxant function after endothelium removal (p < 0.05). In endothelium-denuded vessels, L-NNA attenuated the PVAT vasorelaxant function in control vessels (p < 0.0001). In obesity, incubation with SOD and catalase attenuated PVAT-intact vessel contractility in the presence and absence of endothelium (p < 0.001). In obese humans, SOD [Cu-Zn] (SOD1; fold change -2.4), peroxiredoxin-1 (fold change -2.15) and adiponectin (fold change -2.1) were present in lower abundances than in healthy controls. <b><i>Conclusions:</i></b> Incubation with SOD and catalase restores PVAT vasorelaxant function in animal obesity. In the rodent model, obesity-induced PVAT damage is independent of endothelium and is in part due to reduced NO bioavailability within PVAT. Loss of PVAT function correlates with rising BP in our animal obesity model. In keeping with our hypothesis of inflammation-induced damage to PVAT function in obesity, there are lower levels of SOD1, peroxiredoxin-1 and adiponectin in obese human PVAT

Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis

Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation

Viewing angles in some selected BL Lac objects

A selected subset of BL Lac objects were monitored with VLBI techniques at multifrequencies. Apparent superlumJnal motion and X-rays were detected in all of the monitored sources. From the observational data, kinematic parameters, geometric parameters and beaming effects for the 'core' of the selected BL Lac objects have been estimated. Our results indicate that some BL Lacs have large Lorentz factors and small viewing angles; relativistic beaming effects are strongly present in these sources. On the other hand, some BL Lacs have small Lorentz thctors; their viewing angles are quite large. It does not seem possible to avoid the fact that some BL Lac objects are not oriented particularly close to the line of sight. It conflicts with the basic assumption of the accepted theories for explaining the characteristics of BL Lac objects at present. Also, it seems that the BL Lac objects in the class I of the Burdige and Hewitt's classification have larger viewing angles than those int he class II. The whole BL Lac classification could be a misnomer: the sources classified as 'BL Lac objects' are a mixture of physically different populations with different parent objects