In situ measurement of free radical formation during the thermal decomposition of grape seed oil using “spin trapping” and electron paramagnetic resonance spectroscopy

The generation of free radical intermediates as a result of the oxidative degradation of lipid molecules during the heating of grape seed oil has been established by a combination of “spin trapping” and electron paramagnetic resonance spectroscopy. The effects of temperature on the rates of formation and decomposition of the adduct with the spin trapN-t-butyl-α-phenylnitrone (PBN) have been investigated over the temperature range 105–180°C. The results show that PBN can be used for studies of free radical processes in oils in situ in the spectrometer cavity at temperatures up to 180°C.     

Inhibition of ingestive behavior following fourth ventricle bombesin injection in chronic decerebrate rats.

Tested the hypothesis that the effects of 4th ventricle bombesin (BN) injection on feeding require interaction with forebrain neural systems by measuring intraoral sucrose (0.1 M) in tube-fed control and tube-fed supracollicular decerebrate rats after 4th ventricle injections of 1, 5, 10, 20, and 50 ng BN. Fourth ventricle injections of all doses of BN reliably suppressed sucrose intake in both control and chronic decerebrate rats. These results indicate that caudal brain-stem afferent signals produced by 4th ventricle BN injections are integrated by the local neural circuitry of the caudal brain stem, independent of the forebrain systems, to modulate ingestive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.     

The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules

CK2 is a highly pleiotropic Ser/Thr protein kinase that is able to promote cell survival and enhance the tumour phenotype under specific circumstances. We have determined the crystal structure of three new complexes with tetrabromobenzimidazole derivatives that display K(i) values between 0.15 and 0.30 microM. A comparative analysis of these data with those of four other inhibitors of the same family revealed the presence of some highly conserved water molecules in the ATP-binding site. These waters reside near Lys68, in an area with a positive electrostatic potential that is able to attract and orient negatively charged ligands. The presence of this positive region and two unique bulky residues that are typical of CK2, Ile66 and Ile174, play a critical role in determining the ligand orientation and binding selectivity.     

Determination of polyphenolic content and antioxidant activity of kudingcha made from Ilex kudingcha C.J. Tseng

The total polyphenol content and the antioxidant activity of kudingcha made from Ilex kudingcha C.J. Tseng were determined by Folin–Ciocalteu reagent, and DPPH, FRAP, and TEAC methods, respectively. The crude extract (CE) of kudingcha and its four fractions of chloroform (CfF), ethyl acetate (EaF), n-butanol (nBF), and water (WtF) were prepared and subjected to antioxidant evaluation and analysis by high performance liquid chromatography. The extracts of kudingcha contained large amounts of caffeoylquinic acid (CQA) derivatives, including 3-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA, and showed potent antioxidant activity. The antioxidant activities of CE and its fractions decreased in the order of EaF > nBF > CE > WtF > CfF, according to the DPPH assay and FRAP assay, which were the same, with the exception of the rank order of CfF and WtF, as the TEAC assay. Furthermore, a satisfactory correlation between total polyphenol content and antioxidant activity was observed.