1,968 research outputs found

    High fat diet causes depletion of intestinal eosinophils associated with intestinal permeability.

    Get PDF
    The development of intestinal permeability and the penetration of microbial products are key factors associated with the onset of metabolic disease. However, the mechanisms underlying this remain unclear. Here we show that, unlike liver or adipose tissue, high fat diet (HFD)/obesity in mice does not cause monocyte/macrophage infiltration into the intestine or pro-inflammatory changes in gene expression. Rather HFD causes depletion of intestinal eosinophils associated with the onset of intestinal permeability. Intestinal eosinophil numbers were restored by returning HFD fed mice to normal chow and were unchanged in leptin-deficient (Ob/Ob) mice, indicating that eosinophil depletion is caused specifically by a high fat diet and not obesity per se. Analysis of different aspects of intestinal permeability in HFD fed and Ob/Ob mice shows an association between eosinophil depletion and ileal paracelullar permeability, as well as leakage of albumin into the feces, but not overall permeability to FITC dextran. These findings provide the first evidence that a high fat diet causes intestinal eosinophil depletion, rather than inflammation, which may contribute to defective barrier integrity and the onset of metabolic disease

    The Urban Prison: Socioeconomic Vortexes in Latino Neighborhoods

    Get PDF
    This research shows how metropolitan cities throughout the United States are continuously impacting the lives of ethnic minorities. In the United States, Latina/o individuals have been born into socioeconomic vortexes. In other words, they have grown up in areas where secure jobs have disappeared and a variety of other factors force them to live in damaged communities that do not foster economic and social progression. By analyzing several works of literature written by Latina/o authors who lived in barrios that faced these challenges, as well as research addressing crime and the lack of law enforcement in marginalized neighborhoods, we have come to several conclusions. Primarily, there have been purposeful decisions to abandon Latino urban spaces by removing public services and neglecting educational needs. In addition, individuals as well as corporations that offer secure and legitimate jobs have coordinated a systematic departure from low-income Latino neighborhoods. All these factors contribute to the socioeconomic vortex previously mentioned and inflict substantial psychological and sociological harm and economic hardship on the families living in these areas

    Differences in oxylipin profile in psoriasis versus psoriatic arthritis

    Get PDF
    Funding: This work was supported by the National Institutes of Health (R01AR073324 to MG, P30DK063491 to OQ, T32AR064194 to RC, 1R01AR0690000-01 to CR).Oxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers. Consecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1. Twenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without. The AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients

    Momentum for Catalysis: How Surface Reactions Shape the RuO2 Flat Surface State

    Get PDF
    The active (110) surface of the benchmark oxygen evolution catalyst RuO2 spans a flat-band surface state (FBSS) between the surface projections of its Dirac nodal lines (DNLs) that define the electronic properties of this functional semimetal. Monitoring well-known surface adsorption processes of H2, O2, NO, and CO by in operando angle-resolved photoemission spectroscopy, we selectively modify the oxidation state of individual Ru surface sites and identify the electronic nature of the FBSS: stabilized by bridging oxygen Obr pz, the FBSS disperses along ⟨001⟩ oriented chains of bridging Rubr 4dz2 orbitals, collapses upon Obr removal, yet remains surprisingly unaffected by the oxidation state of the undercoordinated 1f-cus-Ru species. This directly reflects in the ability of RuO2(110) to oxidize CO and H2 along with its inability to oxidize NO, demonstrating the FBSS’s active role in catalytic charge transfer processes at the oxygen bridge sites. Our synergetic approach provides momentum-resolved insights to the interplay of a catalyst’s delocalized electronic band structure and the localized orbitals of its surface reactantsa route toward a microscopic understanding of heterogeneous catalysis

    NCoR Repression of LXRs Restricts Macrophage Biosynthesis of Insulin-Sensitizing Omega 3 Fatty Acids

    Get PDF
    SummaryMacrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies

    Probing the earliest phases in the formation of massive galaxies with simulated HST+JWST imaging data from Illustris

    Full text link
    We use the Illustris-1 simulation to explore the capabilities of the Hubble\textit{Hubble} and James Webb Space Telescope\textit{James Webb Space Telescope} data to analyze the stellar populations in high-redshift galaxies, taking advantage of the combined depth, spatial resolution, and wavelength coverage. For that purpose, we use simulated broad-band ACS, WFC3 and NIRCam data and 2-dimensional stellar population synthesis (2D-SPS) to derive the integrated star formation history (SFH) of massive (M>1010_{\ast}>10^{10}\,M_{\odot}) simulated galaxies at 11011110^{11}\,M_{\odot} galaxy. In particular, we explore the potential of HST and JWST datasets reaching a depth similar to those of the CANDELS and ongoing CEERS observations, respectively, and concentrate on determining the capabilities of this dataset for characterizing the first episodes in the SFH of local M>1011_{\ast}>10^{11}\,M_{\odot} galaxies by studying their progenitors at z>1z>1. The 2D-SPS method presented in this paper has been calibrated to robustly recover the cosmic times when the first star formation episodes occurred in massive galaxies, i.e., the first stages in their integrated SFHs. In particular, we discuss the times when the first 1% to 50% of their total stellar mass formed in the simulation. We demonstrate that we can recover these ages with typical median systematic offset of less than 5% and scatter around 20%-30%. According to our measurements on Illustris data, we are able to recover that local M>1011_{\ast}>10^{11}\,M_{\odot} galaxies would have started their formation by z=16z=16, forming the first 5% of their stellar mass present at z1z \sim 1 by z=4.5z=4.5, 10% by z=3.7z=3.7, and 25% by z=2.7z=2.7.Comment: 28 pages, 13 figures, 4 tables. ApJ in press. Summary of changes from original submission: the major change is that we now include in Sec. 6 the comparison of the results obtained for our sample of massive 1 < z < 4 progenitors with those obtained by considering all massive galaxies at 1 < z < 4 in the simulated images. Several figures and sections have been update
    corecore