Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis

The ability of an organism to sense and store nutrients is vital to survival. The liver is the major organ responsible for converting excess dietary carbohydrate to lipid for storage. An elegant molecular pathway has evolved that allows increased glucose flux into hepatocytes to generate a signaling molecule, xylulose 5-phosphate, that triggers rapid changes in glycolytic enzyme activities and nuclear import of a transcription factor, ChREBP, which coordinates the transcriptional regulation of enzymes that channel the glycolytic end-products into lipogenesis. Further understanding of this metabolic cascade should provide insights on conditions such as fatty liver, obesity, and the metabolic syndrome

The use of a battery of tracking tests in the quantitative evaluation of neurological function

A tracking test battery has been applied in a drug trail designed to compare the efficacy of L-DOPA and amantadine to that of L-DOPA and placebo in the treatment of 28 patients with Parkinson's disease. The drug trial provided an ideal opportunity for objectively evaluating the usefulness of tracking tests in assessing changes in neurologic function. Evaluating changes in patient performance resulting from disease progression and controlled clinical trials is of great importance in establishing effective treatment programs

End of One Way

Describes the role of three South Minneapolis community-based organizations. Demonstrates how the organizations form partnerships and share leadership with their communities. Explores a set of themes derived from each example of community engagement

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Quantitative evaluation of neuropharmacological trials

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116906/1/cpt1974153229.pd

Identification of Basophils as a Major Source of Hepatocyte Growth Factor in Chronic Myeloid Leukemia: A Novel Mechanism of BCR-ABL1-Independent Disease Progression

AbstractChronic myeloid leukemia (CML) is a hematopoietic neoplasm characterized by the Philadelphia chromosome and the related BCR-ABL1 oncoprotein. Acceleration of CML is usually accompanied by basophilia. Several proangiogenic molecules have been implicated in disease acceleration, including the hepatocyte growth factor (HGF). However, little is known so far about the cellular distribution and function of HGF in CML. We here report that HGF is expressed abundantly in purified CML basophils and in the basophil-committed CML line KU812, whereas all other cell types examined expressed only trace amounts of HGF or no HGF. Interleukin 3, a major regulator of human basophils, was found to promote HGF expression in CML basophils. By contrast, BCR-ABL1 failed to induce HGF synthesis in CML cells, and imatinib failed to inhibit expression of HGF in these cells. Recombinant HGF as well as basophil-derived HGF induced endothelial cell migration in a scratch wound assay, and these effects of HGF were reverted by an anti-HGF antibody as well as by pharmacologic c-Met inhibitors. In addition, anti-HGF and c-Met inhibitors were found to suppress the spontaneous growth of KU812 cells, suggesting autocrine growth regulation. Together, HGF is a BCR-ABL1-independent angiogenic and autocrine growth regulator in CML. Basophils are a unique source of HGF in these patients and may play a more active role in disease-associated angiogenesis and disease progression than has so far been assumed. Our data also suggest that HGF and c-Met are potential therapeutic targets in CML

A New Biology: A Modern Perspective on the Challenge of Closing the Gap between the Islands of Knowledge

This paper discusses the rebirth of the old quest for the principles of biology along the discourse line of machine-organism disanalogy and within the context of biocomputation from a modern perspective. It reviews some new attempts to revise the existing body of research and enhance it with new developments in some promising fields of mathematics and computation. The major challenge is that the latter are expected to also answer the need for a new framework, a new language and a new methodology capable of closing the existing gap between the different levels of complex system organization

Body composition and venison quality of farmed red deer (<i>Cervus elaphus</i>) hinds reared on grass, <i>papilionaceous</i> or mixed pasture paddocks

Red deer (Cervus elaphus) hinds (n=3×10) of identical initial body weight (BW, ca. 68&thinsp;kg) were reared on a monocotyledonous grass (G group), on a grass–papilionaceous (GP group) or on pure papilionaceous pasture each of 2&thinsp;ha (P group) for 219 d. At the end of the experiment carcass tissue composition was assessed by means of computer tomography, slaughter value and meat quality were characterized and tissue – longissimus thoracis et lumborum (LTL), thigh and liver – samples were taken for fatty acid composition analysis. The primary aim was to assess nutrition-driven differences. Hinds of group P provided higher final BW (101&thinsp;kg vs. 90 and 91.9&thinsp;kg in groups G and GP, respectively) and higher BW gain (32.6&thinsp;kg during the total period vs. 22.4 and 22.1&thinsp;kg). The carcass weight exceeded those of the other groups significantly (68.8&thinsp;kg vs. 59.3 and 63.2&thinsp;kg), while there was no difference among groups in the perirenal fat weight and red color tone (a*) of the LTL. Groups G and P differed significantly in the LTL weight (highest in P), its dripping loss (lowest in G), lightness (L; highest in P) and yellow color tone (b*). In the thigh muscle, LTL and liver the highest proportion of fatty acid CLA9c11t was reached on the G pasture, and the same trend was true for docosahexaenoic acid (DHA , C22:6 n3) in the muscles. The n6&thinsp;∕&thinsp;n3 fatty acid ratio was the highest on the P pasture in the liver and both muscles. The liver incorporated the highest proportion of linoleic acid (C18:2 n6) and converted it rather effectively to arachidonic acid (C20:4 n6), coupled with the lowest α-linolenic acid presence. In conclusion, concerning muscle mass production, group P proved to be the most advantageous pasture; meanwhile LTL meat quality factors (dripping loss, DHA proportion, pH, color) were more favorable on the G pasture.</p