Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis

Encephalitic listeriosis in sheep is a life-threatening disease. However, little is known about the cytokine response and their predictive value in this disease. The aim of present study was to assess the prognostic significance of Tumor Necrosis Factor-α (TNF-α), Interleukin-12(p40) (IL-12 p40), Interleukin-6 (IL-6), and Interleukin 10 (IL-10) levels in cerebrospinal fluid (CSF) in sheep with encephalitic listeriosis. Fifty-nine ewes in 14 flocks were diagnosed clinically as having listeriosis. CSF was collected and subjected to bacteriological examination and estimation of selected cytokines. Twenty-eight ewes were confirmed to be infected with Listeria monocytogenes. Based on antimicrobial sensitivity test, sheep were treated and the outcome was recorded as survivors (n = 10) and non-survivors (n = 18). Cutoff points for CSF cytokines were determined by Receiver operating characteristic analysis (ROC). Association between levels of CSF cytokines and outcome of listeriosis was assessed by logistic regression. TNF-α, IL-6 and IL-12(p40) levels as well as TNF-α/IL-10 ratio were significantly higher in non-survivors than survivors (p = 0.002, 0.0021, 0.0033, and 0.001, respectively). However, IL-10 level was significantly lower in non-survivors than survivors (p = 0.0058). ROC analysis revealed that IL-6 and TNF-α/IL-10 ratio had the highest AUC values (0.98, 0.984, respectively). Final multivariate logistic regression model showed that TNF-α/IL-10 ratio was the only variable that has predictive value for mortality in diseased sheep (p: 0.001; OR: 7.2; 95% CI: 5.7–9.8). TNF-α showed a positive correlation with IL-12β (r = 0.917) and IL-6 (r = 0.965). IL-12 (p40) showed also a positive correlation with IL-6 (r = 0.906). However, IL-10 showed a negative correlation with TNF-α (r = −0.915), IL-12(p40) (r = −0.790), and IL-6 (r = −0.902). In conclusion, TNF-α/IL-10 ratio may provide predictive information about outcome of encephalitic listeriosis in sheep.     

Nitric oxide inhibitory constituents from Siegesbeckia pubescens

Two new sesquiterpenoids (1 and 2) and a new ent-pimarane type diterpenoid (3), together with eighteen known compounds (4–21), were isolated from the whole plants of Siegesbeckia pubescens. The structures of the new compounds were determined on the basis of 1D-, 2D NMR and HRESIMS data. All compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Of these, highly oxygenated germacrane type sesquiterpenoids (1–2 and 13–14) showed significant inhibitory effects with IC₅₀ values ranging from 3.9 to 16.8 μM.     

Stable isotope proxies for evaluating biodiversity in stream biota

Differences in δ¹³C and δ¹⁵N values in stream biota are caused by several environmental conditions. Variations in abundance, species richness and the assemblage structure of stream biota are also caused by several environmental conditions. Hence, abundance, species richness and the assemblage structure of stream biota are expected to be strongly correlated with the differences in value of stable isotopes. In this study, the gaps in δ¹³C and δ¹⁵N between periphyton and charr are discussed in terms of the abundance, genus richness, and assemblage of benthic invertebrates at each site. Gaps in δ¹³C between periphyton and charr were strongly correlated with some aspects of mountainous area and the genus richness of benthic invertebrates at each site. The gaps in δ¹⁵N between periphyton and charr were strongly correlated with the abundance and assemblage structure of benthic invertebrates at the location tested. The δ¹³C values of predators were correlated with some aspects of mountainous area and the assemblage structure of the benthic invertebrates. The δ¹⁵N values of predators were correlated with genus richness and the assemblage structure of the benthic invertebrates. These results suggest that the value gaps in δ¹³C and δ¹⁵N can be used to assess biodiversity and could provide indices for estimating the biodiversity in a stream.     

Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167

Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and in lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H₂O₂) levels. These changes correlated with an increase in serine-phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be protein kinase Cδ (PKCδ) dependent. Mass spectrometry identified serine 167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from Escherichia coli or transiently transfected COS-7 cells demonstrated that S167D catalase had an increased ability to degrade H₂O₂ compared to the wild-type enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist tezosentan. S167 is located on the dimeric interface, suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel filtration to examine the multimeric structure of recombinant wild-type and S167D catalase. We found that recombinant wild-type catalase was present as a mixture of monomers and dimers, whereas S167D catalase was primarily tetrameric. Further, the incubation of wild-type catalase with PKCδ was sufficient to convert wild-type catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity.     

The effect of semi-natural habitats on aphids and their natural enemies across spatial and temporal scales

Semi-natural habitats in agricultural landscapes are generally assumed to enhance the biological control of insect pests based on native beneficial insects, by providing alternative prey and hosts, resources and refuges for overwintering. We hypothesized that natural enemies of winter wheat aphids should arrive sooner in fields near semi-natural habitats. We compared aphid, hoverfly (larvae and eggs) and parasitized aphid (mummies) abundances in 54 winter wheat fields located in southern France from 2003 to 2007. Six surveys were recorded each spring and were split into the early period (defined as the period before the peak of aphid growth) and the late period (after the peak). The wheat fields differed by their surrounding landscape composition measured as the proportion of semi-natural habitats (woods, hedges and grasslands), at three different spatial scales: 200 m, 500 m, and 1200 m. Despite great variability in abundance data between years, the abundance of hoverflies appeared more sensitive to landscape composition than aphid abundance was. Early abundance for both aphids and hoverflies was positively related to wood cover, but not late abundance in spring. The abundance of hoverflies was positively related to hedge and grassland cover at all spatial scales and both periods considered. Aphid parasitism was higher near hedges at the small spatial scale late in the spring. Our results confirmed that higher proportions of semi-natural habitats in agricultural landscapes enhance the biological control of pests, but this effect depends on the spatial scale, the time period in the spring and the natural enemies considered.     

Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies

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