Impairment in the telocyte/CD34+ stromal cell network in human rheumatoid arthritis synovium

Telocytes (TCs)/CD34⁺ stromal cells have recently emerged as peculiar interstitial cells detectable in a variety of organs throughout the human body. TCs are typically arranged in networks establishing unique spatial relationships with neighbour cells and likely contributing to the maintenance of tissue homeostasis by both cell-to-cell contacts and releasing extracellular vesicles. Hence, TC defects are being increasingly reported in different pathologies, such as chronic inflammatory and fibrotic conditions. In this regard, TCs/CD34⁺ stromal cells have been shown to constitute an intricate interstitial network in the subintimal area of the normal human synovial membrane, but whether they are altered in chronic synovitis has yet to be explored. We therefore undertook a morphologic study to compare the distribution of TCs/CD34⁺ stromal cells between normal synovium and chronically inflamed synovium from patients with rheumatoid arthritis (RA) by using CD34 immunohistochemistry and CD31/CD34 double immunofluorescence. CD34 immunostaining revealed that, at variance with normal synovium, the inflamed and hyperplastic RA synovial tissue was nearly or even completely devoid of TCs/CD34⁺ stromal cells. Double immunofluorescence confirmed that almost all CD34⁺ tissue components detectable in RA synovium were blood vessels coexpressing CD31, while a widespread network of CD31⁻/CD34⁺ TCs was clearly evident in the whole sublining layer of normal synovium. In the context of the emerging diverse roles of TCs/CD34⁺ stromal cells in the regulation of tissue homeostasis and structure, the remarkable impairment in their networks herein uncovered in RA synovium may suggest important pathophysiologic implications that will be worth investigating further.     

Seroprevalence of Chikungunya virus and living conditions in Feira de Santana,Bahia-Brazil

BackgroundChikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition.Methodology/principal findingsWe conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033).Conclusions/significanceThe seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.     

Adiponectin reverses β-Cell damage and impaired insulin secretion induced by obesity

Obesity significantly decreases life expectancy and increases the incidence of age-related dysfunctions, including β-cell dysregulation leading to inadequate insulin secretion. Here, we show that diluted plasma from obese human donors acutely impairs β-cell integrity and insulin secretion relative to plasma from lean subjects. Similar results were observed with diluted sera from obese rats fed ad libitum, when compared to sera from lean, calorically restricted, animals. The damaging effects of obese circulating factors on β-cells occurs in the absence of nutrient overload, and mechanistically involves mitochondrial dysfunction, limiting glucose-supported oxidative phosphorylation and ATP production. We demonstrate that increased levels of adiponectin, as found in lean plasma, are the protective characteristic preserving β-cell function; indeed, sera from adiponectin knockout mice limits β-cell metabolic fluxes relative to controls. Furthermore, oxidative phosphorylation and glucose-sensitive insulin secretion, which are completely abrogated in the absence of this hormone, are restored by the presence of adiponectin alone, surprisingly even in the absence of other serological components, for both the insulin-secreting INS1 cell line and primary islets. The addition of adiponectin to cells treated with plasma from obese donors completely restored β-cell functional integrity, indicating the lack of this hormone was causative of the dysfunction. Overall, our results demonstrate that low circulating adiponectin is a key damaging element for β-cells, and suggest strong therapeutic potential for the modulation of the adiponectin signaling pathway in the prevention of age-related β-cell dysfunction.     

The Papanicolaou Stain for Negri Bodies in Paraffin Sections

Paraffin sections ot the hippocampus (Amnion's horn) from brains of dogs and cows, fixed in sublimate-alcohol (HgCl₂, sat. aq., 1 vol.; absolute alcohol, 2 vol.) were stained by Papanicolaou's (1942) method for vaginal smears. Negri bodies were stained a bright rose color, with nucleoli dark blue. Even though the orange G were omitted, good staining of Negri bodies was obtained. Eliminating this dye simplifies the technic without impairing its effectiveness in the diagnosis of rabies, but the complete staining gives a somewhat more colorful and brighter histologic picture.     

Publication date and author spelling for the hidden angelshark Squatina occulta

Two dates of publication have been associated with the hidden angelshark Squatina occulta. Additionally, the name of the second author of this species has been cited with different spellings in different publications. Both inconsistencies are addressed in this study. It is suggested that the hidden angelshark be consistently cited as Squatina occulta Vooren & da Silva 1991.     

Characterization of epoxide hydrolase activity in shape Alternaria alternata f. sp. shape lycopersici. Possible involvement in toxin production

Using trans-diphenylpropane oxide (tDPPO) as a substrate, we measured epoxide hydrolase (EH) activity in subcellular fractions of Alternaria alternata f. sp. lycopersici (Aal), a fungus that produces host-specific toxins. The activity was mainly (>99.5%) located in the soluble fraction (100,000 × g supernatant) with the optimum pH at 7.4. An increase of toxin production between days 3 and 9 found in a Aal liquid culture over a 15 days period was concomitant with a period of high EH activity. EH activity remained constant during the same period in an Alternaria alternata culture, a fungus which does not produce toxin. In vivo treatment of Aal culture with the peroxisome proliferator clofibrate stimulated EH activity by 83% and enhanced toxin production 6.3 fold. Both 4-fluorochalcone oxide (4-FCO) and (2S,3S)-(-)-3-(4-nitrophenyl)-glycidol (SS-NPG) inhibited EH activity in vitro with a IM₅₀f 23 ± 1 μM and 72 ± 19 μM, respectively. The possible physiological substrate 9,10-epoxystearic acid was hydrolyzed more efficiently by Aal sEH than the model substrates trans- and cis-stilbene oxide (TSO and CSO) and trans- and cis-diphenylpropane oxide (tDPPO and cDPPO). This revised version was published online in June 2006 with corrections to the Cover Date.     

A targeted metabolomics assay for cardiac metabolism and demonstration using a mouse model of dilated cardiomyopathy

Metabolomics can be performed either as an ‘open profiling’ tool where the aim is to measure, usually in a semi-quantitative manner, as many metabolites as possible or perform ‘closed’ or ‘targeted’ analyses where instead a pre-defined set of metabolites are measured. Targeted methods can be designed to be more sensitive and quantitative and so are particularly appropriate to systems biology for quantitative models of systems or when metabolomics is performed in a hypothesis driven manner to test whether a particular pathway is perturbed. We describe a targeted metabolomics assay that quantifies a broad range of over 130 metabolites relevant to cardiac metabolism including the pathways of the citric acid cycle, fatty acid oxidation, glycolysis, the pentose phosphate pathway, amino acid metabolism, the urea cycle, nucleotides and reactive oxygen species using tandem mass spectrometry to produce quantitative, sensitive and robust data. This assay is illustrated by profiling cardiac metabolism in a lamin A/C (Lmna) mouse model of dilated cardiomyopathy (DCM). The model of DCM was characterised by increases in concentrations of proline and methyl-histidine suggestive of increased myofibrillar and collagen degradation, as well as decreases in a number of citric acid cycle intermediates and carnitine derivatives indicating reduced energy metabolism in the dilated heart. These assays could be used for any other cardiac or cardiovascular disease in that they cover central core metabolism and key pathways involved in cardiac metabolism, and may provide a general start for many mammalian systems.