The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

Purpose In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Patient and methods Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. Results LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. Conclusion LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits

Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes

<p>Abstract</p> <p>Background</p> <p>Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM), glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr^-/-) compared to wild-type littermates.</p> <p>Results</p> <p>Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes) using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88) for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels.</p> <p>Conclusions</p> <p>In sum, the results of this study suggest that the complete ablation of hepatic glucagon receptor function results in major metabolic alterations in the liver, which, while promoting improved glycemic control, may be associated with adverse lipid changes.</p

Proteome and Membrane Fatty Acid Analyses on Oligotropha carboxidovorans OM5 Grown under Chemolithoautotrophic and Heterotrophic Conditions

Oligotropha carboxidovorans OM5 T. (DSM 1227, ATCC 49405) is a chemolithoautotrophic bacterium able to utilize CO and H2 to derive energy for fixation of CO2. Thus, it is capable of growth using syngas, which is a mixture of varying amounts of CO and H2 generated by organic waste gasification. O. carboxidovorans is capable also of heterotrophic growth in standard bacteriologic media. Here we characterize how the O. carboxidovorans proteome adapts to different lifestyles of chemolithoautotrophy and heterotrophy. Fatty acid methyl ester (FAME) analysis of O. carboxidovorans grown with acetate or with syngas showed that the bacterium changes membrane fatty acid composition. Quantitative shotgun proteomic analysis of O. carboxidovorans grown in the presence of acetate and syngas showed production of proteins encoded on the megaplasmid for assimilating CO and H2 as well as proteins encoded on the chromosome that might have contributed to fatty acid and acetate metabolism. We found that adaptation to chemolithoautotrophic growth involved adaptations in cell envelope, oxidative homeostasis, and metabolic pathways such as glyoxylate shunt and amino acid/cofactor biosynthetic enzymes

Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c.

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and PAR4 reactivity and were inversely correlated with PCTP mRNA levels, PC-TP protein levels and PAR4 reactivity. miR-376c regulated the expression of PC-TP in human megakaryocytes. A disproportionately high number of microRNAs that were differentially expressed by race and PAR4 reactivity, including miR-376c, are encoded in the DLK1-DIO3 locus and were expressed at lower levels in platelets from black subjects. These results suggest that PC-TP contributes to the racial difference in PAR4-mediated platelet activation, indicate a genomic contribution to platelet function that differs by race and emphasize a need to consider the effects of race when developing anti-thrombotic drugs

Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review

The inflammation process in the human body plays a central role in the pathogenesis of many chronic diseases. In addition, reactive oxygen species (ROS) exert potentially a decisive role in human body, particularly in physiological and pathological process. The chronic inflammation state could generate several types of diseases such as cancer, atherosclerosis, diabetes mellitus and arthritis, especially if it is concomitant with high levels of pro-inflammatory markers and ROS. The respiratory burst of inflammatory cells during inflammation increases the production and accumulation of ROS. However, ROS regulate various types of kinases and transcription factors such nuclear factor-kappa B which is related to the activation of pro-inflammatory genes. The exact crosstalk between pro-inflammatory markers and ROS in terms of pathogenesis and development of serious diseases is still ambitious. Many studies have been attempting to determine the mechanistic mutual relationship between ROS and pro-inflammatory markers. Therefore hereby, we review the hypothetical relationship between ROS and pro-inflammatory markers in which they have been proposed to initiate cancer, atherosclerosis, diabetes mellitus and arthritis