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.     

The effect of caffeine,different fixation regimes and low temperature on microtubules in the cells of higher plants

Caffeine, (1:3:7-tri-methyl-xanthine), either as a prefixation treatment or included with glutaralde-hyde as the primary fixative, destroys or disorganises the microtubules associated with the formation of secondary walls in fibres from the flowering stem of the grass Lolium temulentum L. There is no observable effect of caffeine treatment on the microtubules associated with primary wall formation in collenchyma and young fibres from L. temulentum or in root cap cells of Zea mays L. and Phaseolus vulgaris L. The microtubules associated with primary wall formation are destroyed by cold treatment but not those associated with secondary wall formation. Tannic acid included in the fixative shows the microtubules associated with secondary wall formation in fibres of L. temulentum to be composed of 13 subunits. Treatment with lanthanum hydroxide does not stain the core or the halo of the microtubules.Abbreviation PIPES Piperazine N-N- bis 2 ethanol sulphonic acid The Grassland Research Institute is financed through the Agricultural Research Council     

Clinical Problems: Progressive Neurological Deficits in Primary Polycythaemia

Patients with primary polycythaemia may present clinical features which lead to an erroneous diagnosis of intracerebral neoplasm. Three such cases are described in detail in this report.     

Postnatal D2-CAM/N-CAM Sialylation State Is Controlled by a Developmentally Regulated Golgi Sialyltransferase

Abstract: Golgi-enriched fractions have been isolated from rat brain of increasing postnatal age and defined by electron microscopy and distribution of marker enzymes. The expression of sialyltransferase activity associated with these fractions has been demonstrated to developmentally decrease and this appeared to be, in part, dependent on endogenous competitive inhibition. The developmental regulation of this activity paralleled the sialylation state of the neural cell adhesion molecule (D2-CAM/N-CAM) and could be demonstrated to be capable of endogenously sialylating this protein in the isolated Golgi fractions. In 12-day-old animals the majority of the transferred [¹⁴C]sialic acid was found to be associated with the high-molecular-weight [>200 kilodaltons (kd)] form of D2-CAM/N-CAM, indicative of the protein having been heavily sialylated. Sialylation of the individual D2-CAM/N-CAM polypeptides was also demonstrated in both 12-day and adult animals and transfer was evident only in the 180-kd and 115-kd components and not in the 140-kd component. In contrast, Golgi-enriched fractions prepared from adult animals showed little capability of heavily sialylating D2-CAM/N-CAM to any significant extent.     

Invertebrate predator-prey body size relationships: an explanation for upper triangular food webs and patterns in food web structure?

Summary It has been suggested by Cohen and Newman (1985) that many of the patterns in published food webs can be derived from a stochastic model in which the species are arranged in a trophic hierarchy (the cascade model). We suggest that, if predators are larger than their prey, a trophic hierarchy can be generated on the basis of body size Empirical evidence from the literature shows that there is a positive relationship between predator and prey size for a range of invertebrates and that predators are usually larger than their prey. Using experimental data on an aquatic food web we show that body size can lead to the type of trophic hierarchy used in the cascade model, suggesting that many food web patterns may be a product of body size. This conclusion is discussed with respect to the limitations of the food web data and the relationship between static and dynamic models of web structure.     

Differentiation-Dependent Sialylation of Individual Neural Cell Adhesion Molecule Polypeptides During Postnatal Development

The postnatal sialylation of individual neural cell adhesion molecule (N-CAM) polypeptides by a developmentally regulated sialyltransferase in Golgi-enriched fractions isolated from rat brain is described. The 120-kilodalton polypeptide of N-CAM was found to be sialylated at each developmental age examined. This was in contrast to the 140- and 180-kilodalton N-CAM polypeptides which were only sialylated until postnatal day 10 and from postnatal day 12, respectively. Immunoblotting procedures demonstrated that all N-CAM polypeptides were expressed in the Golgi fractions at each developmental stage examined. The heavily sialylated "embryonic" form of N-CAM was found to be reexpressed at postnatal days 10 and 12, a time coincident with extensive fibre outgrowth. The "embryonic" form of N-CAM incorporated similar amounts of [14C]sialic acid into its constituent polypeptides reflecting the difference in sialic acid to protein ratio, as this form of N-CAM was virtually undetectable in the immunoblots of postnatal material.     

Food-web models that generate constant predator-prey ratios

Summary An approximately constant ratio of number of predator species/number of prey species is observed in several natural communities, although the exact value of the ratio may vary with habitat and the types of organisms in the food web. We test the hypothesis that a constant predator/prey ratio can be generated by what Holt (1977) terms apparent competition and what Jeffries and Lawton (1984) call competition for enemy-free space. We create simple, two trophic-level communities by drawing species of predators and prey at random from a species pool, simulating their interactions using Lotka-Volterra models. The simulated food webs converge over successive periods of invasion and extinction to locally stable systems with approximately constant ratios of number of predator species/number of prey species, despite varying initial conditions. As expected, predator/prey ratios take different values depending upon the biology of the simulated species. We conclude that apparent competition between prey species via shared enemies may be one mechanism whereby approximately constant predator/prey ratios are generated in natural communities.     

Physical property improvements of a pellicular biocatalyst

The thermal stability of an immobilization technique using a pellicular latex matrix was examined in a packed-bed column reactor. The stability was found to vary with liquid flow rate, the type of latex, temperature of operation, and the amount of yeast cells. Adjusting these parameters and introducing particulate inorganic fillers strengthened the latex matrix and improved the thermal stability. Optimization of this immobilization technique resulted in a procedure that allowed latex polymers to be mechanically stable at temperatures up to 50°C. The biological viability of this improved immobilization scheme was demonstrated through the production of L-aspartic acid by immobilized cells of E. coli.