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.     

Climate change and cereal aphids: the relative effects of increasing CO2 and temperature on aphid population dynamics

Experimental evidence regarding the responses of cereal aphids to rising atmospheric CO₂ has been ambiguous. Some studies suggest increased population sizes under future CO₂ levels, others suggest decreased population sizes, and still others suggest little or no difference. Recently, Newman et al. (2003) constructed a general mathematical model of the aphid–grass interaction to investigate whether or not we should, in fact, expect a general aphid response to rising CO₂. They concluded that aphid populations are likely to be larger under future CO₂ concentrations if soil N levels are high, the aphid species' nitrogen requirement is low and the aphid species' density‐dependent response in winged morph production is weak. In that model, and in field experiments, CO₂ concentration influences aphid population dynamics through the effect it has on plant quality. However, future CO₂ concentrations are also likely to be accompanied by higher ambient temperatures, a combination that has received little focus to date. In the present paper, the Newman et al. model is used to consider the combined effects of increased CO₂ concentrations and temperature on aphid population sizes. It is concluded that, when both factors are elevated, aphid population dynamics will be more similar to current ambient conditions than expected from the results of experiments studying either factor alone. This result has important implications for future experimentation.     

Interaction between CO2 enrichment and salinity stress in the C4 non-halophyte Andropogon glomeratus (Walter) BSP

Abstract Increasing atmospheric CO₂ may result in alleviation of salinity stress in salt-sensitive plants. In order to assess the effect of enriched CO₂ on salinity stress in Andropogon glomeratus, a C₄ non-halophyte found in the higher regions of salt marshes, plants were grown at 350, 500, and 650 cm³ m^?3 CO₂ with 0 or 100 mol m^?3 NaCl watering treatments. Increases in leaf area and biomass with increasing CO₂ were measured in salt-stressed plants, while decreases in these same parameters were measured in non-salt-stressed plants. Tillering increased substantially with increasing CO₂ in salt-stressed plants, resulting in the increased biomass. Six weeks following initiation of treatments, there was no difference in photosynthesis on a leaf area basis with increasing CO₂ in salt-stressed plants, although short-term increases probably occurred. Stomatal conductance decreased with increasing CO₂ in salt-stressed plants, resulting in higher water-use efficiency, and may have improved the diurnal water status of the plants. Concentrations of Na⁺ and Cl^? were higher in salt stressed-plants while the converse was found for K ⁺. There were no differences in leaf ion content between CO₂ treatments in the salt-stressed plants. Decreases in photosynthesis in salt-stressed plants occurred primarily as a result of decreased internal (non-stomatal) conductance.     

Microbial communities colonising nutrient-enriched marine sediment

Sediment cores were set up to study microbial colonisation and interactions on marine sand grains under enrichment conditions. Cores were enriched with photosynthetic media in the light and dark (PL, PD) and heterotrophic media in the light and dark (HL, HD), and were incubated for 25 days. Sediment chlorophylls were then measured by acetone extraction, viable heterotrophic bacteria by plate counts, and numbers of cells mm^–2 sand grain surface by s.e.m. Chlorophyll a occurred in all sediments but was highest in the PL sediment. Bacteriochlorophyll a was only observed in the HL sediment. Heterotrophic viable counts were high in the HL and HD sediments. Dense growth of diatoms and blue-green algae, and a marine fungal Thraustochytrid sp. occurred on PL grains. The blue-green alga Schizothrix was often associated with the diatom Amphora on PL grains. Many different bacteria grew on HL and HD grains and some unusual colony and cell morphologies were recorded (Caulobacter, Flexibacter, polymer strands). Characteristic flakey material sometimes occurred in hollows on grains. The results are discussed in relation to microbial communities in low energy sedimentary environments.     

Comparison of the three-dimensional structure of two human rhinoviruses (HRV2 and HRV14)

An attempt has been made to build a model of human rhinovirus 2 (HRV2) based on the known human rhinovirus 14 (HRV14) structure. HRV2 was selected because its amino acid sequence is known and because it belongs to the minor rhinovirus receptor class as compared to HRV14, which belongs to the major class. Initial alignment of HRV2 with HRV14 based on the primary sequence and the knowledge of the three-dimensional structure of HRV14 showed that the most probable position of the majority of insertions and deletions occurred in the vicinity of the neutralizing immunogenic sites (NIm). Out of a total of 855 amino acids present in one copy of each of the capsid proteins VP1 through VP4 of HRV14, 411 are different between the two viruses. There are also 6 amino acid residues inserted and 14 residues deleted in HRV2 relative to HRV14. Examination of amino acid interactions showed several cases of conservation of function, e.g., salt bridges or the filling of restricted space. The largest variation amongst the residues lining the canyon, the putative receptor binding site, was in the carboxy-terminal residues of VP1.     

Evidence for a periodic excretion of nitrogen by roots of grass-legume associations

Diurnal variation in ion content of the solution bathing roots of two plants growing together in sand culture was analysed for three pairs of grass-legume species (Lolium multiflorum andTrifolium pratense; Zea mays andGlycine hispida; Avena sativa andVicia sativa) and their monospecific controls. Biomass and nitrogen content of plants were determined. Ion concentration (NO ₃ ⁻ , NO ₂ ⁻ , NH ₄ ⁺ , and K⁺) and pH of root solutions were measured for Lolium-Trifolium plant pairs and controls at 6 hours intervals over 36 h, starting at 8 am within a circadian cycle. Root solutions were regularly depleted in NO ₃ ⁻ by the grasses (Lolium-Lolium control) throughout the cycle. For associations involving the legume (Lolium-Trifolium and Trifolium-Trifolium), NO ₃ ⁻ depletion was followed by NO ₃ ⁻ enrichment at night, from late afternoon to early morning; the enrichment was more marked for the Lolium-Trifolium association. Solutions which did not contain NO ₂ ⁻ ions, were enriched by trace amounts of NH ₄ ⁺ ions, largely depleted in K⁺ and alkalanized for all associations throughout the cycle. Repeating the experiment with the three pairs of species at the vegetative phase of development confirmed the previous results: NO ₃ ⁻ enrichment during the night for associations with legumes. When the experiment was repeated with older plants which had almost completed their flowering stage, depletion only was observed and no NO ₃ ⁻ enrichment. These data suggest that NO ₃ ⁻ enrichment results from N excretion from active nodulated roots of the legume, accounting for the increase in both biomass and nitrogen content of the companion grass in grass-legume association. The quantitative importance and periodicity of nitrogen excretion as well as the origin of nitrate enrichment are discussed.     

Propionate metabolism in a methanogenic enrichment culture. Direct reductive carboxylation and acetogenesis pathways

Abstract Serial dilutions of methanogenic sludges in propionate medium gave a methanogenic non-acetoclastic enrichment degrading 1 mol of propionate to 1.6 mol of acetate and 0.17 mol of methane, with a transient accumulation of butyrate. NMR recordings showed the conversion of [2-¹³C]- and [3-¹³C]-propionate to [3-¹³C]- and [4-¹³C]-butyrate, respectively, thus demonstrating a reductive carboxylation of propionate to butyrate. The labelling found in the accumulated acetate and fermentation balances also suggested that reductive carboxylation was the major pathway involved in propionate conversion to acetate.     

Coated nuts as an enrichment device to elicit tool use in tufted capuchins (Cebus apella)

The present paper describes a simple technique that hardens the shell of nuts and makes the use of a tool to crack them open more compelling. Walnuts were coated with a dough of sawdust and nontoxic white glue in different combinations; they were tested for hardness by using machines normally used to test different kinds of wood. Data on relative hardness for uncoated walnuts and walnuts coated with dough of two different combinations are presented. The coated walnuts were significantly harder to break than the uncoated ones, whereas no significant difference was found when comparing the hardness of two types of coated walnuts. Furthermore, observations on a captive group of tufted capuchins (Cebus apella) are described. The monkeys needed significantly more time to break open the coated walnuts. Early results show that coated walnuts may favor acquistion of tool use skills in a juvenile capuchin.