A putative GDP–GTP exchange factor is required for development of the excretory cell in Caenorhabditis elegans

The Caenorhabditis elegans excretory cell extends tubular processes, called canals, along the basolateral surface of the epidermis. Mutations in the exc-5 gene cause tubulocystic defects in this canal. Ultrastructural analysis suggests that exc-5 is required for the proper placement of cytoskeletal elements at the apical epithelial surface. exc-5 encodes a protein homologous to guanine nucleotide exchange factors and contains motif architecture similar to that of FGD1, which is responsible for faciogenital dysplasia. exc-5 interacts genetically with mig-2, which encodes Rho GTPase. These results suggest that EXC-5 controls the structural organization of the excretory canal by regulating Rho family GTPase activities.     

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.     

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.     

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

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The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1

Mutations in immunoglobulin µ-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30° and 10°, respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations.     

Fine‐scale variation within urban landscapes affects marking patterns and gastrointestinal parasite diversity in red foxes

1. Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine‐scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence.
2. Here, we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine‐scale variation in socio‐economic and ecological variables can affect red fox (Vulpes vulpes) marking behavior, gastrointestinal (GI) parasite prevalence, and parasite community diversity.
3. We found that the presence and abundance of red fox fecal markings were nonuniformly distributed across greenspaces and instead were dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness, and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas.
4. Our results suggest that fine‐scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores.

     

Characterization of the microtubule movement produced by sea urchin egg kinesin

We have used an in vitro assay to characterize some of the motile properties of sea urchin egg kinesin. Egg kinesin is purified via 5'-adenylyl imidodiphosphate-induced binding to taxol-assembled microtubules, extraction from the microtubules in ATP, and gel filtration chromatography (Scholey, J. M., Porter, M. E., Grissom, P. M., and McIntosh, J. R. (1985) Nature 318, 483-486). This partially purified kinesin is then adsorbed to a glass coverslip, mixed with microtubules and ATP, and viewed by video-enhanced differential interference contrast microscopy. The microtubule translocating activity of the purified egg kinesin is qualitatively similar to the analogous activity observed in crude extracts of sea urchin eggs and resembles the activity of neuronal kinesin with respect to both the maximal rate (greater than 0.5 micron/s) and the direction of movement. Axonemes glide on a kinesin-coated coverslip toward their minus ends, and kinesin-coated beads translocate toward the plus ends of centrosome microtubules. Sea urchin egg kinesin is inhibited by high concentrations of SH reagents ([N-ethylmaleimide] greater than 3-5 mM), vanadate greater than 50 microM, and [nonhydrolyzable nucleotides] greater than or equal to [MgATP]. The nucleotide requirement of sea urchin egg kinesin is fairly broad (ATP greater than GTP greater than ITP), and the rate of microtubule movement increases in a saturable fashion with the [ATP]. We conclude that the motile activity of egg kinesin is indistinguishable from that of neuronal kinesin. We propose that egg kinesin may be associated with microtubule-based motility in vivo.     

Implantation and Recovery of Long-Term Archival Transceivers in a Migratory Shark with High Site Fidelity

We developed a long-term tagging method that can be used to understand species assemblages and social groupings associated with large marine fishes such as the Sand Tiger shark Carcharias taurus. We deployed internally implanted archival VEMCO Mobile Transceivers (VMTs; VEMCO Ltd. Nova Scotia, Canada) in 20 adult Sand Tigers, of which two tags were successfully recovered (10%). The recovered VMTs recorded 29,646 and 44,210 detections of telemetered animals respectively. To our knowledge, this is the first study to demonstrate a method for long-term (~ 1 year) archival acoustic transceiver tag implantation, retention, and recovery in a highly migratory marine fish. Results show low presumed mortality (n = 1, 5%), high VMT retention, and that non-lethal recovery after almost a year at liberty can be achieved for archival acoustic transceivers. This method can be applied to study the social interactions and behavioral ecology of large marine fishes.