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.     

Food quality for Eudiaptomus gracilis: the importance of particular highly unsaturated fatty acids

1. Development times and survival of nauplii and copepodites of the freshwater calanoid Eudiaptomus gracilis were measured on comparably sized Cryptomonas sp. and two strains of Chlamydomonas reinhardii under food saturated conditions (1 mg C L−1) to investigate the nutritional quality of these algae.
2.  Cryptomonas sp. supported complete ontogenesis of nauplii to adults, whereas both strains of C. reinhardii were inadequate for the development of nauplii and copepodites and resulted in high mortality. The nutritional deficiency of both strains of C. reinhardii was compensated for by Cryptomonas sp. when the latter constituted ≥50% of dietary carbon. Pulses of Cryptomonas sp. had a similar compensatory effect.
3. In comparison to Cryptomonas sp., both strains of C. reinhardii were deficient in the three highly unsaturated fatty acids (HUFAs) stearidonic, eicosapentaenoic and docosahexaenoic acid. We manipulated the fatty acid content of C. reinhardii by externally adding these three HUFAs to the alga so that the fatty acid profile resembled that of Cryptomonas sp. This supplementation did not improve food quality, however, indicating that the nutritional deficiency of both strains of C. reinhardii for the ontogenesis of E. gracilis is not due to a lack of these three HUFAs.     

Interaction between the light quality and flowering time pathways in Arabidopsis

Flowering in Arabidopsis is accelerated by a reduced ratio of red light to far-red light (R/FR), which indicates the proximity of competitive vegetation. By exploiting the natural genetic variation in flowering time responses to low R/FR, we obtained further insight into the complex pathways that fine-tune the transition to flowering in Arabidopsis. The Bla-6 ecotype does not flower significantly earlier in response to low R/FR, but is still able to display other features of shade avoidance, suggesting branching of low R/FR signalling. Here we show that the muted flowering response of Bla-6 is due to high levels of the floral repressor FLOWERING LOCUS C (FLC), conferred by a combination of functional FLC and FRIGIDA ( FRI ) alleles with a 'weak' FY allele. The Bla-6 FY allele encodes a protein with a corrupted WW binding domain, and we provide evidence that this locus plays a key role in the natural variation in light quality-induced flowering in Arabidopsis. In Bla-6, FLC blocks promotion to flowering by reduced R/FR by inhibiting expression of the floral integrator FLOWERING LOCUS T ( FT ) in a dose-dependent manner. Reduction of FLC removes this obstruction, and Bla6 plants then exhibit strong induction of FT and flower early in response to a low R/FR signal. This paper illustrates the intricate interaction of environmental signals and genetic factors to regulate flowering in Arabidopsis.     

Host‐size decisions of female parasitoid wasps seeking hidden hosts

1. Choice of host size may play a critical role in parasitoid success, a task that takes on added complications when dealing with concealed hosts, but most such studies of insect behaviour have only taken place in the laboratory. 2. This study investigates the success of a wasp (Alabagrus texanus: Braconidae) in finding host caterpillars Herpetogramma theseusalis (Crambidae) of the most effectively handled size hidden in shelters, in both the field and the laboratory. 3. First, the study tested wasp preference and success in parasitizing large, middle‐sized and small caterpillars (> 5, 3–5, < 3 mm) presented in the open, one at a time, in the laboratory. The wasps attacked (inserted or attempted to insert their ovipositor) a higher proportion of middle‐sized (3–5 mm) caterpillars compared with either small (< 3 mm) or large (> 5 mm) caterpillars. Naïve wasps attacked large caterpillars more often than did experienced wasps. Wasps responded to increasing caterpillar size by increasing the number of legs used to pin their prey rather than by increasing handling time. 4. The frequencies of visits to shelters in the field containing a majority of either large or middle‐sized caterpillars were then compared, followed by a test providing the wasps with similar choices under controlled laboratory conditions. Wasps most frequently visited shelters containing a majority of middle‐sized caterpillars both in the field and under controlled laboratory conditions. 5. The combined results confirmed that the wasps can size‐select their hosts both in the field and in laboratory tests.     

Behavior of adult and young grassland songbirds at fledging

The behavior of adults and young at the time of fledging is one of the least understood aspects of the breeding ecology of birds. Current hypotheses propose that fledging occurs either as a result of parent‐offspring conflict or nestling choice. We used video recordings to monitor the behavior of nestling and adult grassland songbirds at the time of fledging. We observed 525 nestlings from 166 nests of 15 bird species nesting in grasslands of Alberta, Canada, and Wisconsin, USA. Overall, 78% of nestlings used terrestrial locomotion for fledging and 22% used wing‐assisted locomotion. Species varied in propensity for using wing‐assisted locomotion when fledging, with nestling Grasshopper Sparrows (Ammodramus savannarum) and Henslow's Sparrows (Centronyx henslowii) often doing so (47% of fledgings) and nestling Song Sparrows (Melospiza melodia), Common Yellowthroats (Geothlypis trichas), and Chestnut‐collared Longspurs (Calcarius ornatus) rarely doing so (3.5% of fledgings). For 390 fledging events at 127 nests, camera placement allowed adults near nests to be observed. Of these, most young fledged (81.5%) when no adult was present at nests. Of 72 fledging events that occurred when an adult was either at or approaching a nest, 49 (68.1%) involved feeding. Of those 49 fledgings, 30 (62.1%) occurred when one or more nestlings jumped or ran from nests to be fed as an adult approached nests. The low probability of nestlings fledging while an adult was at nests, and the tendency of young to jump or run from nests when adults did approach nests with food minimize opportunities for parents to withhold food to motivate nestlings to fledge. These results suggest that the nestling choice hypothesis best explains fledging by nestlings of ground‐nesting grassland songbirds, and fledging results in families shifting from being place‐based to being mobile and spatially dispersed.     

Models of annual cycles in lentic water bodies

A discussion of mathematical modelling of water quality, including a summary of the parameters considered, a comparison of the two major model types (stochastic and deterministic) and a review of the validation process, is presented. A water quality model currently being developed is discussed and a list of ecological models already developed is given.     

The role of protein quality control in mitochondrial protein homeostasis under oxidative stress

Mitochondria contribute significantly to the cellular production of ROS. The deleterious effects of increased ROS levels have been implicated in a wide variety of pathological reactions. Apart from a direct detoxification of ROS molecules, protein quality control mechanisms are thought to protect protein functions in the presence of elevated ROS levels. The reactivities of molecular chaperones and proteases remove damaged polypeptides, maintaining enzyme activities, thereby contributing to cellular survival both under normal and stress conditions. We characterized the impact of oxidative stress on mitochondrial protein homeostasis by performing a proteomic analysis of isolated yeast mitochondria, determining the changes in protein abundance after ROS treatments. We identified a set of mitochondrial proteins as substrates of ROS‐dependent proteolysis. Enzymes containing oxidation‐sensitive prosthetic groups like iron/sulfur clusters represented major targets of stress‐dependent degradation. We found that several proteins involved in ROS detoxification were also affected. We identified the ATP‐dependent protease Pim1/LON as a major factor in the degradation of ROS‐modified soluble polypeptides localized in the matrix compartment. As Pim1/LON expression was induced significantly under ROS treatment, we propose that this protease system performs a crucial protective function under oxidative stress conditions.     

The effect of wilting on palatability of plants to Schistocerca gregaria,the desert locust

Summary Previous work has shown that host choice by acridids (grasshoppers and locusts) is sensitive to alterations in host quality. In particular, reduced plant water content has been found to increase palatability of certain plant species. To determine if this phenomenon is general, and to gain preliminary information on causes, turgid and wilted plant material of forty-one species was tested using nymphs of the desert locust, Schistocerca gregaria. Twelve plant species (29%) had increased and five (12%) had decreased palatability (as measured by meal size) when wilted. Among fifteen families tested, the increases occurred in six, the decreases in three. The greatest change occurred in Taraxacum officinale; further tests on this plant revealed the increase to be continuous, rising with decreasing water content. The behavioral observations combined with the pattern of the results across plant species suggest that changes are due to alterations in specific deterrents or stimulants, rather than to decreased water content or increased concentrations of amino acids and/or sugars. The implications of these results for understanding drought-associated population outbreaks are discussed.