Lipopolysaccharide Regulates the Macrophage RNA-Binding Proteome.

RNA-protein interactions within cellular signaling pathways have significant modulatory effects on RNA binding proteins' (RBPs') effector functions. During the innate immune response, specific RNA-protein interactions have been reported as a regulatory layer of post-transcriptional control. We investigated changes in the RNA-bound proteome of immortalized mouse macrophages (IMM) following treatment with lipopolysaccharide (LPS). Stable isotope labeling by amino acids in cell culture (SILAC) of cells followed by unbiased purification of RNP complexes at two time points after LPS stimulation and bottom-up proteomic analysis by LC-MS/MS resulted in a set of significantly affected RBPs. Global RNA sequencing and LFQ proteomics were used to characterize the correlation of transcript and protein abundance changes in response to LPS at different time points with changes in protein-RNA binding. Il1α, MARCKS, and ACOD1 were noted as RBP candidates involved in innate immune signaling. The binding sites of the RBP and RNA conjugates at amino acid resolution were investigated by digesting the cross-linked oligonucleotide from peptides remaining after elution using Nuclease P1. The combined data sets provide directions for further studies of innate immune signaling regulation by RBP interactions with different classes of RNA.

Omics and systems view of innate immune pathways.

Multiomics approaches to studying systems biology are very powerful techniques that can elucidate changes in the genomic, transcriptomic, proteomic, and metabolomic levels within a cell type in response to an infection. These approaches are valuable for understanding the mechanisms behind disease pathogenesis and how the immune system responds to being challenged. With the emergence of the COVID-19 pandemic, the importance and utility of these tools have become evident in garnering a better understanding of the systems biology within the innate and adaptive immune response and for developing treatments and preventative measures for new and emerging pathogens that pose a threat to human health. In this review, we focus on state-of-the-art omics technologies within the scope of innate immunity.

Understanding run-in behavior of diamond-like carbon friction and preventing diamond-like carbon wear in humid air.

The friction behavior of diamond-like carbon (DLC) is very sensitive to the test environment. For hydrogen-rich DLC tested in dry argon and hydrogen, there was always an induction period, so-called "run-in" period, during which the friction coefficient was high and gradually decreased before DLC showed an ultralow friction coefficient (less than 0.01) behavior. Regardless of friction coefficients and hydrogen contents, small amounts of wear were observed in dry argon, hydrogen, oxygen, and humid argon environments. Surprisingly, there were no wear or rubbing scar on DLC surfaces tested in n-pentanol vapor conditions, although the friction coefficient was relatively high among the five test environments. Ex situ X-ray photoelectron and near-edge X-ray absorption fine-structure spectroscopy analyses failed to reveal any differences in chemical composition attributable to the environment dependence of DLC friction and wear. The failure of getting chemical information of oxygenated surface species from the ex situ analysis was found to be due to facile oxidation of the DLC surface upon exposure to air. The removal or wear of this surface oxide layer is responsible for the run-in behavior of DLC. It was discovered that the alcohol vapor can also prevent the oxidized DLC surface from wear in humid air conditions.

Effects of gas adsorption isotherm and liquid contact angle on capillary force for sphere-on-flat and cone-on-flat geometries.

This paper explains the origin of the vapor pressure dependence of the asperity capillary force in vapor environments. A molecular adsorbate layer is readily formed on solid surface in ambient conditions unless the surface energy of the solid is low enough and unfavorable for vapor adsorption. Then, the capillary meniscus formed around the solid asperity contact should be in equilibrium with the adsorbate layer, not with the bare solid surface. A theoretical model incorporating the vapor adsorption isotherm into the solution of the Young-Laplace equation is developed. Two contact geometries--sphere-on-flat and cone-on-flat--are modeled. The calculation results show that the experimentally-observed strong vapor pressure dependence can be explained only when the adsorption isotherm of the vapor on the solid surface is taken into account. The large relative partial pressure dependence mainly comes from the change in the meniscus size due to the presence of the adsorbate layer.

Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat.

Oxidative stress has been directly implicated in hypertension and myocardial remodelling, two pathologies fundamental to the development of chronic heart failure. Selenium (Se) can act directly and indirectly as an antioxidant and a lowered Se status leads to a higher risk of cardiovascular disease. This study examined the role of Se on the development of hypertension and subsequent progression to chronic heart failure in spontaneously hypertensive rats (SHR). Three dietary groups were studied: (i) Se-free; (ii) normal Se (50 µg Se/kg food); and (iii) high Se (1000 µg Se/kg food). Systolic blood pressure and echocardiography were used to detect cardiac changes in vivo. At study end, cardiac tissues were assayed for glutathione peroxidase activity, thioredoxin reductase activity, and protein carbonyls. The major finding of this study was the high heart failure-related mortality rate in SHRs fed an Se-free diet (70%). Normal and high levels of dietary Se resulted in higher survival rates of 78 and 100%, respectively. Furthermore, high dietary Se was clearly associated with lower levels of cardiac oxidative damage and increased antioxidant expression, as well as a reduction in disease severity and mortality in the SHR.