Protists, which are single-celled eukaryotes, critically influence the ecology and chemistry of marine ecosystems, but genome-based studies of these organisms have lagged behind those of other ...microorganisms. However, recent transcriptomic studies of cultured species, complemented by meta-omics analyses of natural communities, have increased the amount of genetic information available for poorly represented branches on the tree of eukaryotic life. This information is providing insights into the adaptations and interactions between protists and other microorganisms and macroorganisms, but many of the genes sequenced show no similarity to sequences currently available in public databases. A better understanding of these newly discovered genes will lead to a deeper appreciation of the functional diversity and metabolic processes in the ocean. In this Review, we summarize recent developments in our understanding of the ecology, physiology and evolution of protists, derived from transcriptomic studies of cultured strains and natural communities, and discuss how these novel large-scale genetic datasets will be used in the future.
About the Authors: Nolwenn M. Dheilly * E-mail: nolwenn.dheilly@stonybrook.edu (NMD); jmartinez@bigelow.org (JMM) Affiliation: School of Marine and Atmospheric Sciences, Stony Brook University, Stony ...Brook, New York, United States of America ORCID logo http://orcid.org/0000-0002-3675-5013 Joaquín Martínez Martínez * E-mail: nolwenn.dheilly@stonybrook.edu (NMD); jmartinez@bigelow.org (JMM) Affiliation: Bigelow Laboratory for Ocean Sciences, East Boothbay, Maine, United States of America ORCID logo http://orcid.org/0000-0002-2295-0264 Karyna Rosario Affiliation: College of Marine Science, University of South Florida, Saint Petersburg, Florida, United States of America ORCID logo http://orcid.org/0000-0001-9847-4113 Paul J. Brindley Affiliations Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, United States of America, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America ORCID logo http://orcid.org/0000-0003-1765-0002 Raina N. Fichorova Affiliation: Genital Tract Biology Division, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ORCID logo http://orcid.org/0000-0002-9980-5735 Jonathan Z. Kaye Affiliation: Gordon and Betty Moore Foundation, Palo Alto, California, United States of America Kevin D. Kohl Affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ORCID logo http://orcid.org/0000-0003-1126-2949 Laura J. Knoll Affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America Julius Lukeš Affiliation: Institute of Parasitology, Biology Centre, Czech Academy of Sciences and Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic ORCID logo http://orcid.org/0000-0002-0578-6618 Susan L. Perkins Affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York, United States of America ORCID logo http://orcid.org/0000-0002-5400-5662 Robert Poulin Affiliation: Department of Zoology, University of Otago, Dunedin, New Zealand Lynn Schriml Affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ORCID logo http://orcid.org/0000-0001-8910-9851 Luke R. Thompson Affiliations Department of Biological Sciences and Northern Gulf Institute, University of Southern Mississippi, Hattiesburg, Mississippi, United States of America, Ocean Chemistry and Ecosystems Division, Atlantic Oceanographic and Meteorological Laboratory, National Oceanic and Atmospheric Administration, La Jolla, California, United States of America ORCID logo http://orcid.org/0000-0002-3911-1280 Citation: Dheilly NM, Martínez Martínez J, Rosario K, Brindley PJ, Fichorova RN, Kaye JZ, et al. Methods to tackle the grand challenges of parasite microbiome research. https://doi.org/10.1371/journal.ppat.1008028.t001 A primary advantage of a centralized platform like the PMP is the collation of large aggregates of associated metadata that can be harnessed to uncover, and eventually understand, patterns of microbial diversity and ecology 40, 35. ...detailed metadata associated with each study and sample are absolutely critical to maximize the utility of each. ...when possible, experimental evolution of parasites and hosts in the presence or absence of the identified microbes can been used to test the effect of specific microbes on the evolution of the system and to identify mechanisms involved in parasite–microbe interaction. The PMP will necessitate both significant funding to conduct challenging research as well as engagement from the community to provide high-quality samples and to share detailed and accurate metadata information. ...we propose constituting a community of researchers that meet annually for workshops and symposia.
TOX is a DNA-binding factor required for development of CD4(+) T cells, natural killer T cells and regulatory T cells. Here we document that both natural killer (NK) cell development and lymphoid ...tissue organogenesis were also inhibited in the absence of TOX. We found that the development of lymphoid tissue-inducer cells, a rare subset of specialized cells that has an integral role in lymphoid tissue organogenesis, required TOX. Tox was upregulated considerably in immature NK cells in the bone marrow, consistent with the loss of mature NK cells in the absence of this nuclear protein. Thus, many cell lineages of the immune system share a TOX-dependent step for development.
Early innate lymphoid progenitors (EILPs) have recently been identified in mouse adult bone marrow as a multipotential progenitor population specified toward innate lymphoid cell (ILC) lineages, but ...their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic approaches collectively establish EILPs as an intermediate progenitor between ALPs and ILCps. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4
T
2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show ...induction of a molecularly distinct subset of activated lung ILC2, termed ILC2
. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC2
are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC2
. In vivo, IL-2 enhances ILC2
generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC2
population contracts after cessation of stimulation in vivo, with maintenance of a subset that can be recalled by restimulation, analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population.
This Pillars of Immunology article is a commentary on three pivotal articles: “Nuclear factor of activated T cells contains Fos and Jun,” an article written by J. Jain, P. G. McCaffrey, V. E. ...Valge-Archer, and A. Rao, and published in Nature, in 1992, https://www.nature.com/articles/356801a0; “The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun,” written by J. Jain, P. G. McCaffrey, Z. Miner, T. K. Kerppola, J. N. Lambert, G. L. Verdine, T. Curran, and A. Rao, and published in Nature, in 1993, https://www.nature.com/articles/365352a0; and “Isolation of the cyclosporin-sensitive T cell transcription factor NFATp,” written by P. G. McCaffrey, C. Luo, T. K. Kerppola, J. Jain, T. M. Badalian, A. M. Ho, E. Burgeon, W. S. Lane, J. N. Lambert, T. Curran, et al., and published in Science, in 1993, https://www.science.org/doi/10.1126/science.8235597.
Aim of the Review
relatively new European Union regulations on children’s medicines have emphasised the need for scientists to consider paediatric populations during drug development. This requires ...an understanding of the physiology in the paediatric population compared to that of adults. In this review, data cited in the public literature on the gastrointestinal (GI) physiology that could affect drug absorption have been summarised to draw attention to some of the differences between adults and paediatric populations that can make predicting the pharmacokinetics of oral drugs in the paediatric population a complex task.
Method
a search for relevant articles was conducted using EMBASE, MEDLINE (through PubMed) and The National Institute for Public Health and the Environment. Additional journals were found from the references in the initial search results. Furthermore, a selection of common textbooks was used to fill in gaps in physiology data or understanding not covered by the journal articles found. Only data obtained from healthy individuals was used.
Results
information on the pH and transit time along the GI tract, as well as other GI physiology data was collated and summarised. There was less data available in the literature on the younger population partly as a consequence of the challenging ethics of carrying out invasive tests on healthy children.
Discussion and Conclusion
it was found that considerable variability in physiology exists within the paediatric population. The pH and transit time of the GI tract varies with age, with the greatest changes occurring during the neonate’s first month. Other GI physiology also varies with age potentially having an impact on drug absorption. This review highlights the variability of paediatric physiological values within the literature, indicating the difficulty in performing measurements in the paediatric population as well as the natural variability that exists in this age group.
Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence ...the host’s physiological capacities; however, the identity and functional role(s) of key members of the microbiome (“core microbiome”) in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems’ capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts’ plastic and adaptive responses to environmental change requires (i) recognizing that individual host–microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.
The soft tissues of many fossil vertebrates preserve evidence of melanosomes-micron-scale organelles that inform on integumentary coloration and communication strategies. In extant vertebrates, ...however, melanosomes also occur in internal tissues. Hence, fossil melanosomes may not derive solely from the integument and its appendages. Here, by analyzing extant and fossil frogs, we show that non-integumentary melanosomes have high fossilization potential, vastly outnumber those from the skin, and potentially dominate the melanosome films preserved in some fossil vertebrates. Our decay experiments show that non-integumentary melanosomes usually remain in situ provided that carcasses are undisturbed. Micron-scale study of fossils, however, demonstrates that non-integumentary melanosomes can redistribute through parts of the body if carcasses are disturbed by currents. Collectively, these data indicate that fossil melanosomes do not always relate to integumentary coloration. Integumentary and non-integumentary melanosomes can be discriminated using melanosome geometry and distribution. This is essential to accurate reconstructions of the integumentary colours of fossil vertebrates.
Self-reactive CD8
T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we ...characterize the transcriptional and epigenetic landscape of self-reactive CD8
T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8
T cells emerging from acute viral infection. We find that autoimmune CD8
T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling. This self-reactive CD8
T cell fate depends on the transcriptional regulation by the DNA-binding HMG-box protein TOX which remodels more than 400 genomic regions including loci such as Tcf7, which is central to stemness of CD8
T cells. Continuous exposure to CNS self-antigen sustains TOX levels in self-reactive CD8
T cells, whereas genetic ablation of TOX in CD8
T cells results in shortened persistence of self-reactive CD8
T cells in the inflamed CNS. Our study establishes and characterizes the genetic differentiation program enabling chronic T cell-driven immunopathology in CNS autoimmunity.
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