Recent studies suggest that the sterol metabolic network participates in the interferon (IFN) antiviral response. However, the molecular mechanisms linking IFN with the sterol network and the ...identity of sterol mediators remain unknown. Here we report a cellular antiviral role for macrophage production of 25-hydroxycholesterol (cholest-5-en-3β,25-diol, 25HC) as a component of the sterol metabolic network linked to the IFN response via Stat1. By utilizing quantitative metabolome profiling of all naturally occurring oxysterols upon infection or IFN-stimulation, we reveal 25HC as the only macrophage-synthesized and -secreted oxysterol. We show that 25HC can act at multiple levels as a potent paracrine inhibitor of viral infection for a broad range of viruses. We also demonstrate, using transcriptional regulatory-network analyses, genetic interventions and chromatin immunoprecipitation experiments that Stat1 directly coupled Ch25h regulation to IFN in macrophages. Our studies describe a physiological role for 25HC as a sterol-lipid effector of an innate immune pathway.
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► Macrophage PRR sensing of virus or IFN activation induce 25HC synthesis and secretion ► Stat1 rapidly binds and activates the promoter of cholesterol-25-hydroxylase (Ch25h) ► 25HC exerts multilevel antiviral function for a range of different viruses ► 25HC is an intrinsic paracrine and autocrine effector of the IFN antiviral response
The remote and hostile Southern Ocean is home to a diverse and rich community of life that thrives in an environment dominated by glaciations and strong currents. Marine biological studies in the ...region date back to the nineteenth century, but despite this long history of research, relatively little is known about the complex interactions between the highly seasonal physical environment and the species that inhabit the Southern Ocean. Oceanographically, the Southern Ocean is a major driver of global ocean circulation and plays a vital role in interacting with the deep water circulation in each of the Pacific, Atlantic, and Indian oceans. The Census of Antarctic Marine Life and the Scientific Committee on Antarctic Research Marine Biodiversity Information Network (SCAR-MarBIN) have strived to coordinate and unify the available scientific expertise and biodiversity data to improve our understanding of Southern Ocean biodiversity. Taxonomic lists for all marine species have been compiled to form the Register of Antarctic Marine Species, which currently includes over 8,200 species. SCAR-MarBIN has brought together over 1 million distribution records for Southern Ocean species, forming a baseline against which future change can be judged. The sample locations and numbers of known species from different regions were mapped and the depth distributions of benthic samples plotted. Our knowledge of the biodiversity of the Southern Ocean is largely determined by the relative inaccessibility of the region. Benthic sampling is largely restricted to the shelf; little is known about the fauna of the deep sea. The location of scientific bases heavily influences the distribution pattern of sample and observation data, and the logistical supply routes are the focus of much of the at-sea and pelagic work. Taxa such as mollusks and echinoderms are well represented within existing datasets with high numbers of georeferenced records. Other taxa, including the species-rich nematodes, are represented by just a handful of digital records.
Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the ...crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8-12 somite stage. By integrating spatial context and multiplexed transcriptional measurements with two single-cell transcriptome atlases, we characterize cell types across the embryo and demonstrate that spatially resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain-hindbrain boundary (MHB) and the developing gut tube. We uncover axes of cell differentiation that are not apparent from single-cell RNA-sequencing (scRNA-seq) data, such as early dorsal-ventral separation of esophageal and tracheal progenitor populations in the gut tube. Our method provides an approach for studying cell fate decisions in complex tissues and development.
Oxysterol research: a brief review Griffiths, William J; Wang, Yuqin
Biochemical Society transactions,
04/2019, Letnik:
47, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In the present study, we discuss the recent developments in oxysterol research. Exciting results have been reported relating to the involvement of oxysterols in the fields of neurodegenerative ...disease, especially in Huntington's disease, Parkinson's disease and Alzheimer's disease; in signalling and development, in particular, in relation to Hedgehog signalling; and in cancer, with a special focus on (25R)26-hydroxycholesterol. Methods for the measurement of oxysterols, essential for understanding their mechanism of action
, and valuable for diagnosing rare diseases of cholesterol biosynthesis and metabolism are briefly considered.
Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists, biologists, and physicians for many ...decades, but their exact biological relevance in vivo, other than as intermediates in bile acid biosynthesis, has long been debated. However, in the first quarter of this century, a role for side-chain oxysterols and their C-7 oxidized metabolites has been convincingly established in the immune system. 25-Hydroxycholesterol has been shown to be synthesized by macrophages in response to the activation of Toll-like receptors and to offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol has been shown to act as a chemoattractant to lymphocytes expressing the G protein-coupled receptor Epstein-Barr virus-induced gene 2 and to be important in coordinating the action of B cells, T cells, and dendritic cells in secondary lymphoid tissue. There is a growing body of evidence that not only these two oxysterols but also many of their isomers are of importance to the proper function of the immune system. Here, we review recent findings related to the roles of oxysterols in immunology.
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Reversing defaunation: Restoring species in a changing world Seddon, Philip J.; Griffiths, Christine J.; Soorae, Pritpal S. ...
Science (American Association for the Advancement of Science),
07/2014, Letnik:
345, Številka:
6195
Journal Article
Recenzirano
The rate of biodiversity loss is not slowing despite global commitments, and the depletion of animal species can reduce the stability of ecological communities. Despite this continued loss, some ...substantial progress in reversing defaunation is being achieved through the intentional movement of animals to restore populations. We review the full spectrum of conservation translocations, from reinforcement and reintroduction to controversial conservation introductions that seek to restore populations outside their indigenous range or to introduce ecological replacements for extinct forms. We place the popular, but misunderstood, concept of rewilding within this framework and consider the future role of new technical developments such as de-extinction.
It was thought that the Southern Ocean was relatively free of microplastic contamination; however, recent studies and citizen science projects in the Southern Ocean have reported microplastics in ...deep-sea sediments and surface waters. Here we reviewed available information on microplastics (including macroplastics as a source of microplastics) in the Southern Ocean. We estimated primary microplastic concentrations from personal care products and laundry, and identified potential sources and routes of transmission into the region. Estimates showed the levels of microplastic pollution released into the region from ships and scientific research stations were likely to be negligible at the scale of the Southern Ocean, but may be significant on a local scale. This was demonstrated by the detection of the first microplastics in shallow benthic sediments close to a number of research stations on King George Island. Furthermore, our predictions of primary microplastic concentrations from local sources were five orders of magnitude lower than levels reported in published sampling surveys (assuming an even dispersal at the ocean surface). Sea surface transfer from lower latitudes may contribute, at an as yet unknown level, to Southern Ocean plastic concentrations. Acknowledging the lack of data describing microplastic origins, concentrations, distribution and impacts in the Southern Ocean, we highlight the urgent need for research, and call for routine, standardised monitoring in the Antarctic marine system.
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•The Antarctic marine system is considered pristine compared to other regions.•Microplastics are present in Antarctic waters but available data are scarce.•Local sources of primary microplastic do not explain reported concentrations.•Plastic originating from outside the region may contribute to Antarctic pollution.•Standardised monitoring of microplastic in Antarctic waters is needed urgently.
Implementation studies are often poorly reported and indexed, reducing their potential to inform initiatives to improve healthcare services. The Standards for Reporting Implementation Studies (StaRI) ...initiative aimed to develop guidelines for transparent and accurate reporting of implementation studies. Informed by the findings of a systematic review and a consensus-building e-Delphi exercise, an international working group of implementation science experts discussed and agreed the StaRI Checklist comprising 27 items. It prompts researchers to describe both the implementation strategy (techniques used to promote implementation of an underused evidence-based intervention) and the effectiveness of the intervention that was being implemented. An accompanying Explanation and Elaboration document (published in BMJ Open, doi:10.1136/bmjopen-2016-013318) details each of the items, explains the rationale, and provides examples of good reporting practice. Adoption of StaRI will improve the reporting of implementation studies, potentially facilitating translation of research into practice and improving the health of individuals and populations.
A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS ...classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.
We report time-of-flight measurements on electrons traveling in quantum Hall edge states. Hot-electron wave packets are emitted one per cycle into edge states formed along a depleted sample boundary. ...The electron arrival time is detected by driving a detector barrier with a square wave that acts as a shutter. By adding an extra path using a deflection barrier, we measure a delay in the arrival time, from which the edge-state velocity v is deduced. We find that v follows 1/B dependence, in good agreement with the Eover →×Bover → drift. The edge potential is estimated from the energy dependence of v using a harmonic approximation.
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