Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Tandem application of C-C bond-forming reactions with reductive ozonolysis

Several variants of reductive ozonolysis, defined here as the in situ generation of aldehydes or ketones during ozonolytic cleavage of alkenes, are demonstrated to work effectively in tandem with a number of C-C bond-forming reactions. For reactions involving basic nucleophiles (1,2- addition of Grignard reagents, Wittig or Horner-Emmons olefinations, and directed Aldol reactions of lithium enolates) the one-pot process offers a rapid and high-yielding alternative to traditional two-step protocols

Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii

GTPases of the mouse IRG protein family, mediators of resistance against Toxoplasma gondii in the mouse, are inactivated by a polymorphic kinase of the parasite, resulting in enhanced parasite virulence

Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It

IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii.National Institutes of Health (U.S.)Massachusetts Life Sciences Center (New Investigator Award)National Institute of General Medical Sciences (U.S.) (Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33))Studienstiftung des deutschen VolkesCancer Research Institute (New York, N.Y.)Cleo and Paul Schimmel FoundationBayer HealthcareHuman Frontier Science Program (Strasbourg, France

The Fecal Viral Flora of Wild Rodents

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals

The Rhoptry Proteins ROP18 and ROP5 Mediate Toxoplasma gondii Evasion of the Murine, But Not the Human, Interferon-Gamma Response

The obligate intracellular parasite Toxoplasma gondii secretes effector proteins into the host cell that manipulate the immune response allowing it to establish a chronic infection. Crosses between the types I, II and III strains, which are prevalent in North America and Europe, have identified several secreted effectors that determine strain differences in mouse virulence. The polymorphic rhoptry protein kinase ROP18 was recently shown to determine the difference in virulence between type I and III strains by phosphorylating and inactivating the interferon-γ (IFNγ)-induced immunity-related GTPases (IRGs) that promote killing by disrupting the parasitophorous vacuole membrane (PVM) in murine cells. The polymorphic pseudokinase ROP5 determines strain differences in virulence through an unknown mechanism. Here we report that ROP18 can only inhibit accumulation of the IRGs on the PVM of strains that also express virulent ROP5 alleles. In contrast, specific ROP5 alleles can reduce IRG coating even in the absence of ROP18 expression and can directly interact with one or more IRGs. We further show that the allelic combination of ROP18 and ROP5 also determines IRG evasion and virulence of strains belonging to other lineages besides types I, II and III. However, neither ROP18 nor ROP5 markedly affect survival in IFNγ-activated human cells, which lack the multitude of IRGs present in murine cells. These findings suggest that ROP18 and ROP5 have specifically evolved to block the IRGs and are unlikely to have effects in species that do not have the IRG system, such as humans

The annual update GLODAPv2.2023: the global interior ocean biogeochemical data product

The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface to bottom ocean biogeochemical bottle data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of seawater samples. GLODAPv2.2023 is an update of the previous version, GLODAPv2.2022 (Lauvset et al., 2022). The major changes are as follows: data from 23 new cruises were added. In addition, a number of changes were made to the data included in GLODAPv2.2022. GLODAPv2.2023 includes measurements from more than 1.4 million water samples from the global oceans collected on 1108 cruises. The data for the now 13 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, chlorofluorocarbon-11 (CFC-11), CFC-12, CFC-113, CCl4, and SF6) have undergone extensive quality control with a focus on the systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but converted to World Ocean Circulation Experiment (WOCE) exchange format and (ii) as a merged data product with adjustments applied to minimize bias. For the present annual update, adjustments for the 23 new cruises were derived by comparing those data with the data from the 1085 quality-controlled cruises in the GLODAPv2.2022 data product using crossover analysis. SF6 data from all cruises were evaluated by comparison with CFC-12 data measured on the same cruises. For nutrients and ocean carbon dioxide (CO2), chemistry comparisons to estimates based on empirical algorithms provided additional context for adjustment decisions. The adjustments that we applied are intended to remove potential biases from errors related to measurement, calibration, and data-handling practices without removing known or likely time trends or variations in the variables evaluated. The compiled and adjusted data product is believed to be consistent to better than 0.005 in salinity, 1 % in oxygen, 2 % in nitrate, 2 % in silicate, 2 % in phosphate, 4 µmol kg−1 in dissolved inorganic carbon, 4 µmol kg−1 in total alkalinity, 0.01–0.02 in pH (depending on region), and 5 % in the halogenated transient tracers. The other variables included in the compilation, such as isotopic tracers and discrete CO2 fugacity (fCO2), were not subjected to bias comparison or adjustments. The original data, their documentation, and DOI codes are available at the Ocean Carbon and Acidification Data System of NOAA National Centers for Environmental Information (NCEI), which also provides access to the merged data product. This is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/zyrq-ht66 (Lauvset et al., 2023). These bias-adjusted product files also include significant ancillary and approximated data, which were obtained by interpolation of, or calculation from, measured data. This living data update documents the GLODAPv2.2023 methods and provides a broad overview of the secondary quality control procedures and results

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

GLODAPv2.2022: the latest version of the global interior ocean biogeochemical data product

The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface-to-bottom ocean biogeochemical bottle data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of seawater samples. GLODAPv2.2022 is an update of the previous version, GLODAPv2.2021 (Lauvset et al., 2021). The major changes are as follows: data from 96 new cruises were added, data coverage was extended until 2021, and for the first time we performed secondary quality control on all sulfur hexafluoride (SF6) data. In addition, a number of changes were made to data included in GLODAPv2.2021. These changes affect specifically the SF6 data, which are now subjected to secondary quality control, and carbon data measured on board the RV Knorr in the Indian Ocean in 1994–1995 which are now adjusted using certified reference material (CRM) measurements made at the time. GLODAPv2.2022 includes measurements from almost 1.4 million water samples from the global oceans collected on 1085 cruises. The data for the now 13 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, chlorofluorocarbon-11 (CFC-11), CFC-12, CFC-113, CCl4, and SF6) have undergone extensive quality control with a focus on systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but converted to World Ocean Circulation Experiment (WOCE) exchange format and (ii) as a merged data product with adjustments applied to minimize bias. For the present annual update, adjustments for the 96 new cruises were derived by comparing those data with the data from the 989 quality-controlled cruises in the GLODAPv2.2021 data product using crossover analysis. SF6 data from all cruises were evaluated by comparison with CFC-12 data measured on the same cruises. For nutrients and ocean carbon dioxide (CO2) chemistry comparisons to estimates based on empirical algorithms provided additional context for adjustment decisions. The adjustments that we applied are intended to remove potential biases from errors related to measurement, calibration, and data handling practices without removing known or likely time trends or variations in the variables evaluated. The compiled and adjusted data product is believed to be consistent to better than 0.005 in salinity, 1 % in oxygen, 2 % in nitrate, 2 % in silicate, 2 % in phosphate, 4 µmol kg−1 in dissolved inorganic carbon, 4 µmol kg−1 in total alkalinity, 0.01–0.02 in pH (depending on region), and 5 % in the halogenated transient tracers. The other variables included in the compilation, such as isotopic tracers and discrete CO2 fugacity (fCO2), were not subjected to bias comparison or adjustments. The original data, their documentation, and DOI codes are available at the Ocean Carbon and Acidification Data System of NOAA NCEI (https://www.ncei.noaa.gov/access/ocean-carbon-acidification-data-system/oceans/GLODAPv2_2022/, last access: 15 August 2022). This site also provides access to the merged data product, which is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/1f4w-0t92 (Lauvset et al., 2022). These bias-adjusted product files also include significant ancillary and approximated data, which were obtained by interpolation of, or calculation from, measured data. This living data update documents the GLODAPv2.2022 methods and provides a broad overview of the secondary quality control procedures and results.</p