Multiomic Metabolic Enrichment Network Analysis Reveals Metabolite–Protein Physical Interaction Subnetworks Altered in Cancer

Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings.     

Ultrastructure of oesophageal appendages ("peptonephridia") in enchytraeids (Annelida: Clitellata)

Abstract. Although the oesophageal appendages in the four enchytraeids Enchytrueus crypticus, Fredericia strinta, Buchholzia appendiculata , and Achaeta sp. are quite different from one another in shape and position, their histology and ultrastructure are basically the same. These are intestinal appendages, the lumina of which distally end blind and proximally open into the oesophagus. Almost all of the few cells in their single-layered epithelium have a microvillous, cilia-free border at the apex, facing towards the lumen, and basally comprise an extremely extensive labyrinth. The presence of the latter, composed of very thin cell processes, and of numerous mitochondria identifies the organs as energy-producing and -consuming, transport-active structures. Their possible function as a food-moistening organ or osmoregulatory organ is discussed, and they are compared with other intestinal appendages in enchytraeids and other oligochaetes.     

The effect of DL-propranolol on γ-aminolevulinic acid synthetase activity and urinary excretion of porphyrins in allylisopropylacetamide-induced experimental porphyria

Experimental porphyria was induced in rats by allylisopropylacetamide. DL-Propranolol, a β-adrenergic-receptor blocking agent, significantly reduced the elevated urinary excretion of δ-aminolevulinic acid, porphobilinogen and total porphyrins. DL-Propranolol also partially prevented the increased activity of δ-aminolevulinic acid synthesis in liver homogenates of allylisopropylacetamide-treated rats. It had no effect on the above parameters in normal rats. These findings support the hypothesis that δ-aminolevulinic acid exists in two forms, a constitutive and an inducible one.In order to examine whether the action of the drug was caused by its membrane effect. D-propranolol and quinidine sulphate were used in similar sets of experiments. These drugs had no effect on the abnormal porphyrin metabolism of allylisoprpyl-acetamide-treated rats, indicating that the results obtained with DL-propranolol were not due to its membrane action.     

Genetische Und Zytologische Untersuchungen an Verschiedenen Sippen Von Oenothera Suaveolens

Ohne ZusammenfassungMit 7 Textabbildungen.In ausführlicherer Form und mit zahlreichen Abbildungen als Dissertation bei der Naturwissenschaftlichen Fakultät der Universität München eingereicht.     

Oxidation of fatty acids by Leishmania braziliensis panamensis

Heating cultures of Leishmania braziliensis panamensis (grown at 26 degrees C) to 34 degrees C for 1.5-12 h transformed the cells to an ellipsoidally shaped form. The heat treatment caused an increase in the rate of oxidation of both medium and long chain fatty acids but decreased the rate of oxidation of [1-14C]glucose. The rate of fatty acid oxidation continued to increase for times as long as 20 h after returning the cultures to 26 degrees C. In both the promastigote and heat-induced ellipsoidal forms, the ratio of 14CO2 release from [1-14C]laurate to that from [12-14C]laurate was generally larger than four, whereas this ratio from [1-14C]oleate relative to [10-14C]oleate was approximately two. These data show that metabolic and morphological differentiation begin after a short heat treatment and that some metabolic changes may continue even after the reverse transformation is initiated. The data also suggest that either the omega-terminal portion of the fatty acids is not completely oxidized to acetyl CoA and/or that there are two functional fatty acid oxidation pathways in Leishmania.     

Influence of various soil factors on the effects of ferulic acid on leaf expansion of cucumber seedlings

Summary Cucumber seedlings were grown in a Portsmouth soil-sand system to study how varying soil clay and organic matter content might modify cucumber seedling response to ferulic acid, a reported allelopathic agent. Leaf area expansion of cucumber seedlings, soil respiration, and soil solution concentrations of ferulic acid were monitored. Leaf area, mean absolute rates of leaf expansion, and shoot dry weight of cucumber seedlings were significantly reduced by ferulic acid concentrations ranging from 10 to 70 μg/g dry soil. Ferulic acid was applied every other day, since it rapidly disappeared from soil solution as a result of retention by soil particles, utilization by microbes and/or uptake by roots. The amount of ferulic acid retained (i.e., adsorbed, polymerized,etc.) by soil particles appeared to be secondary to microbial utilization and/or uptake by roots. Varying clay (5.3 to 9.8 g/cup) and organic matter (2.0 to 0.04g/cup) contents of the soil appeared to have little impact on the disappearance of ferulic acid from soil solution under “ideal” growth conditions for cucumber seedlings unless larger amounts of ferulic acid were added to the soil; in this case 200 μg/g. The addition of ferulic acid to the soil materials substantially increased the activity of the soil microbes. This latter conclusion is based on recovery of ferulic acid from soil solution and soil respiration measurements. Paper No. 10347 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, N C 27695-7601. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the product named, nor criticism of similar ones not mentioned.     

Effect of egg cholesterol and dietary fats on plasma lipids, lipoproteins, and apoproteins of normal women consuming natural diets

Nine normal women, 22 to 37 years old, consumed controlled quantities of natural foods to test their responses to dietary cholesterol and saturated fat. All diets contained, as percentage of calories, 14% protein, 31% fat, and 55% carbohydrate. The main sources of polyunsaturated and saturated fats were corn oil and lard, respectively, and egg yolk was used for cholesterol supplementation. All subjects participated in four diet protocols of 15 days duration, and each diet period was separated by 3 weeks without diet control. The first diet (corn) was based on corn oil, had a polyunsaturated to saturated fat ratio (P/S) of 2.14, and contained 130 mg of cholesterol. The second diet (corn+) was identical to the first but contained a total of 875 mg of cholesterol. The third diet (lard) was based on lard, had a P/S ratio of 0.64, and contained 130 mg of cholesterol. The fourth diet (lard+) was identical to the third, but contained 875 mg of cholesterol per day. Changes of the plasma lipid, lipoprotein and apoprotein parameters relative to the corn diet were as follows: the corn+ diet significantly increased total plasma cholesterol, HDL-cholesterol, LDL-cholesterol, and apoB levels; the lard diet significantly increased total cholesterol, HDL-cholesterol, and apoB; and the lard+ diet significantly increased the total cholesterol, HDL-cholesterol, LDL-cholesterol, and apoA-I and apoB levels. There were no significant variations in VLDL-cholesterol, triglyceride, or apoE levels with these diets. The diets affected both the number of lipoprotein particles as well as the composition of LDL and HDL. Compared to the corn diet, cholesterol and saturated fat each increased the number of LDL particles by 17% and 9%, respectively, and the cholesterol per particle by 9%. The combination of saturated fat and cholesterol increased particle number by 18% and particle size by 24%. Switching from lard+ to lard, corn+, or corn diets reduced LDL-cholesterol of the group by 18%, 11%, and 28%, respectively, while a large inter-individual variability was noted. In summary, dietary fat and cholesterol affect lipid and lipoprotein levels as well as the particle number and chemical composition of both LDL and HDL. There is, however, considerable inter-individual heterogeneity in response to diet.