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.     

Positional Assembly of Enzymes on Bacterial Outer Membrane Vesicles for Cascade Reactions

The systematic organization of enzymes is a key feature for the efficient operation of cascade reactions in nature. Here, we demonstrate a facile method to create nanoscale enzyme cascades by using engineered bacterial outer membrane vesicles (OMVs) that are spheroid nanoparticles (roughly 50 nm in diameter) produced by Gram-negative bacteria during all phases of growth. By taking advantage of the fact that OMVs naturally contain proteins found in the outer cell membrane, we displayed a trivalent protein scaffold containing three divergent cohesin domains for the position-specific presentation of a three-enzyme cascade on OMVs through a truncated ice nucleation protein anchoring motif (INP). The positional assembly of three enzymes for cellulose hydrolysis was demonstrated. The enzyme-decorated OMVs provided synergistic cellulose hydrolysis resulting in 23-fold enhancement in glucose production than free enzymes.     

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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Preference and performance of Lepidoptera varies with tree age in juniper woodlands

1. As trees age, they undergo significant physiological and morphological changes. Nevertheless, tree ontogeny and its impacts on herbivores are often overlooked as determinants of plant–herbivore population dynamics and the strength of plant–herbivore interactions. 2. Juniperus (Cupressaceae) is a dominant, long‐lived conifer that serves as the sole host to a specialised assemblage of caterpillars. Over the past 150 years, several juniper species in western North America have expanded their geographic occupancy at local and regional scales, which has resulted in an increase in the number of immature trees on the landscape. Using assays in the laboratory, the effects of tree ontogeny on caterpillar performance and oviposition preference for two juniper specialist caterpillars, Callophrys gryneus (Lycaenidae) and Glena quinquelinearia (Geometridae), were examined. The study considered whether responses to tree ontogeny were consistent across caterpillar species and juniper host species. 3. Tree age was found to be a reliable predictor of caterpillar performance, with caterpillars developing more quickly and growing larger when fed foliage from young trees. Differences in the phytochemical diversity between foliage from trees of different ages might help to explain observed differences in caterpillar performance. Interestingly, the specialist butterfly, C. gryneus, displayed an oviposition preference for foliage from old‐growth Juniperus osteosperma trees, despite the fact that larvae of this species performed poorly on older trees. 4. It is concluded that young juniper trees are an important resource for the specialised Lepidopteran community and that tree ontogeny is an important component of intraspecific variation, which contributes to the structure of plant–herbivore communities.     

Microhabitat nest‐site selection by ducks in the boreal forest

The boreal forest is one of the North America’s most important breeding areas for ducks, but information about the nesting ecology of ducks in the region is limited. We collected microhabitat data related to vegetation structure and composition at 157 duck nests and paired random locations in Alberta’s boreal forest region from 2016 to 2018. We identified fine‐scale vegetation features selected by ducks for all nests, between nesting guilds, and among five species using conditional logistic regression. Ducks in the boreal forest selected nest sites with greater overhead and graminoid cover, but less forb cover than random sites. Characteristics of the nest sites of upland‐ and overwater‐nesting guilds differed, with species nesting in upland habitat selecting nests that provided greater shrub cover and less lateral concealment and species nesting over water selecting nests with less shrub cover. We examined the characteristics of nest sites of American Wigeon (Mareca americana), Blue‐winged Teal (Spatula discors), Green‐winged Teal (Anas crecca), Mallards (Anas platyrhynchos), and Ring‐necked Ducks (Aythya collaris), and found differences among species that may facilitate species coexistence at a regional scale. Our results suggest that females of species nesting in upland habitat selected nest sites that optimized concealment from aerial predators while also allowing detection of and escape from terrestrial predators. Consequently, alteration in the composition and heterogeneity of vegetation and predator communities caused by climate change and industrial development in the boreal forest of Canada may affect the nest‐site selection strategies of boreal ducks.     

Composition and stability of the vervet monkey milk microbiome

The human milk microbiome is vertically transmitted to offspring during the postnatal period and has emerged as a critical driver of infant immune and metabolic development. Despite this importance in humans, the milk microbiome of nonhuman primates remains largely unexplored. This dearth of comparative work precludes our ability to understand how species‐specific differences in the milk microbiome may differentially drive maternal effects and limits how translational models can be used to understand the role of vertically transmitted milk microbes in human development. Here, we present the first culture‐independent data on the milk microbiome of a nonhuman primate. We collected milk and matched fecal microbiome samples at early and late lactation from a cohort of captive lactating vervet monkeys (N = 15). We found that, similar to humans, the vervet monkey milk microbiome comprises a shared community of taxa that are universally present across individuals. However, unlike in humans, this shared community is dominated by the genera Lactobacillus, Bacteroides, and Prevotella. We also found that, in contrast to previous culture‐dependent studies in humans, the vervet milk microbiome exhibits greater alpha‐diversity than the gut microbiome across lactation. Finally, we did not find support for the translocation of microbes from the gut to the mammary gland within females (i.e., “entero‐mammary pathway”). Taken together, our results show that the vervet monkey milk microbiome is taxonomically diverse, distinct from the gut microbiome, and largely stable. These findings demonstrate that the milk microbiome is a unique substrate that may selectively favor the establishment and persistence of particular microbes across lactation and highlights the need for future experimental studies on the origin of microbes in milk.     

Systems genetics analyses predict a transcription role for P2P-R: Molecular confirmation that P2P-R is a transcriptional co-repressor

Background  

The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations.