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 genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens

Mycobacterial pathogens pose a sustained threat to human health. There is a critical need for new diagnostics, therapeutics, and vaccines targeting both tuberculous and nontuberculous mycobacterial species. Understanding the basic mechanisms used by diverse mycobacterial species to cause disease will facilitate efforts to design new approaches toward detection, treatment, and prevention of mycobacterial disease. Molecular, genetic, and biochemical approaches have been widely employed to define fundamental aspects of mycobacterial physiology and virulence. The recent expansion of genetic tools in mycobacteria has further increased the accessibility of forward genetic approaches. Proteomics has also emerged as a powerful approach to further our understanding of diverse mycobacterial species. Detection of large numbers of proteins and their modifications from complex mixtures of mycobacterial proteins is now routine, with efforts of quantification of these datasets becoming more robust. In this review, we discuss the “genetic proteome,” how the power of genetics, molecular biology, and biochemistry informs and amplifies the quality of subsequent analytical approaches and maximizes the potential of hypothesis-driven mycobacterial research. Published proteomics datasets can be used for hypothesis generation and effective post hoc supplementation to experimental data. Overall, we highlight how the integration of proteomics, genetic, molecular, and biochemical approaches can be employed successfully to define fundamental aspects of mycobacterial pathobiology.     

Can genomics clarify the origins of Boreioglycaspis melaleucae in California,USA?

The Australian psyllid Boreioglycaspis melaleucae is a biological control agent of Melaleuca quinquenervia in Florida (USA) but was observed attacking M. quinquenervia trees in southern California (USA). Genotyping revealed the California population matched three of eight Australian haplotypes and all three Florida haplotypes. It remains unclear if the California psyllid population arrived directly from Australia or via Florida.     

Under-ice CO2 and O2 variability in a freshwater lake

Autonomous, in situ sensors for the partial pressure of CO₂(pCO₂) and dissolved oxygen (DO) were deployedin a freshwater lake during the winters of 1997 and 1998 to evaluate magnitudeand sources of variability during ice-covered periods. Gas variability ondiel or shorter time scales was small or undetectable during most of thedeployment periods, only becoming significant prior to ice-out whenrunoff and light penetration increased, promoting convective currents andbiological production. A surprising 7.6 d period oscillation,apparently driven by a baroclinic seiche, dominated the short-termvariability during the first year. The gas trends associated with the seicheoscillations and periodic profile measurements revealed that ice formation ledto gas gradients directly under the ice. Long-term variability wascharacterized by increasing CO₂ and decreasing DO as a consequenceofbiological oxidation of organic matter. The results suggest that both spatialand temporal variability can be significant over intervals which would not beresolved by traditional sampling-based studies.     

Development of Snake Fungal Disease after Experimental Challenge with Ophidiomyces ophiodiicola in Cottonmouths (Agkistrodon piscivorous)

Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.     

The Link between Knowledge,Attitudes and Practices in Relation to Atmospheric Haze Pollution in Peninsular Malaysia

Transboundary haze episodes caused by seasonal forest fires have become a recurrent phenomenon in Southeast Asia, with serious environmental, economic, and public health implications. Here we present a cross-sectional survey conducted among people in Kuala Lumpur and surrounds to assess the links between knowledge, attitudes, and practices in relation to the transboundary haze episodes. Of 305 respondents, 125 were amateur athletes participating in a duathlon event and the remainder were surveyed in an inner-city shopping mall. Across the whole sample, people who possessed more factual information about the haze phenomenon showed significantly higher levels of concern. Duathletes were more knowledgeable than non-duathletes and also more concerned about the negative effects of haze, especially on health. For all people who regularly practice outdoor sports (including people interviewed at the shopping mall), higher levels of knowledge and concerned attitudes translated into a greater likelihood of engaging in protective practices, such as cancelling their outdoor training sessions, while those with greater knowledge were more likely to check the relevant air pollution index on a daily basis. Our results indicate that the provision of accurate and timely information about air quality to residents will translate into beneficial practices, at least among particularly exposed individuals, such as amateur athletes who regularly practice outdoor sports.     

The development of cephalic armor in the tokay gecko (Squamata: Gekkonidae: Gekko gecko)

Armored skin resulting from the presence of bony dermal structures, osteoderms, is an exceptional phenotype in gekkotans (geckos and flap-footed lizards) only known to occur in three genera: Geckolepis, Gekko, and Tarentola. The Tokay gecko (Gekko gecko LINNAEUS 1758) is among the best-studied geckos due to its large size and wide range of occurrence, and although cranial dermal bone development has previously been investigated, details of osteoderm development along a size gradient remain less well-known. Likewise, a comparative survey of additional species within the broader Gekko clade to determine the uniqueness of this trait has not yet been completed. Here, we studied a large sample of gekkotans (38 spp.), including 18 specimens of G. gecko, using X-rays and high-resolution computed tomography for visualizing and quantifying the dermal armor in situ. Results from this survey confirm the presence of osteoderms in a second species within this genus, Gekko reevesii GRAY 1831, which exhibits discordance in timing and pattern of osteoderm development when compared with its sister taxon, G. gecko. We discuss the developmental sequence of osteoderms in these two species and explore in detail the formation and functionality of these enigmatic dermal ossifications. Finally, we conducted a comparative analysis of endolymphatic sacs in a wide array of gekkotans to explore previous ideas regarding the role of osteoderms as calcium reservoirs. We found that G. gecko and other gecko species with osteoderms have highly enlarged endolymphatic sacs relative to their body size, when compared to species without osteoderms, which implies that these membranous structures might fulfill a major role of calcium storage even in species with osteoderms.