39 research outputs found

    Linking interstellar and cometary O₂: a deep search for ¹⁶O¹⁸O in the solar-type protostar IRAS 16293–2422

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    Recent measurements carried out at comet 67P/Churyumov–Gerasimenko (67P) with the Rosetta probe revealed that molecular oxygen, O₂, is the fourth most abundant molecule in comets. Models show that O₂ is likely of primordial nature, coming from the interstellar cloud from which our solar system was formed. However, gaseous O₂ is an elusive molecule in the interstellar medium with only one detection towards quiescent molecular clouds, in the ρ Oph A core. We perform a deep search for molecular oxygen, through the 2₁−0₁ rotational transition at 234 GHz of its ¹⁶O¹⁸O isotopologue, towards the warm compact gas surrounding the nearby Class 0 protostar IRAS 16293–2422 B with the ALMA interferometer. We also look for the chemical daughters of O₂, HO₂, and H₂O₂. Unfortunately, the H₂O₂ rotational transition is dominated by ethylene oxide c-C₂H₄O while HO₂ is not detected. The targeted ¹⁶O¹⁸O transition is surrounded by two brighter transitions at ± 1 km s⁻¹ relative to the expected ¹⁶O¹⁸O transition frequency. After subtraction of these two transitions, residual emission at a 3σ level remains, but with a velocity offset of 0.3−0.5 km s⁻¹ relative to the source velocity, rendering the detection “tentative”. We derive the O₂ column density for two excitation temperatures Tₑₓ of 125 and 300 K, as indicated by other molecules, in order to compare the O₂ abundance between IRAS 16293 and comet 67P. Assuming that ¹⁶O¹⁸O is not detected and using methanol CH₃OH as a reference species, we obtain a [O₂]/[CH₃OH] abundance ratio lower than 2−5, depending on the assumed Tₑₓ, a three to four times lower abundance than the [O₂]/[CH₃OH] ratio of 5−15 found in comet 67P. Such a low O₂ abundance could be explained by the lower temperature of the dense cloud precursor of IRAS 16293 with respect to the one at the origin of our solar system that prevented efficient formation of O₂ in interstellar ices

    Quantitative metabolomics based on gas chromatography mass spectrometry: status and perspectives

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    Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome). By analyzing differences between metabolomes using biostatistics (multivariate data analysis; pattern recognition), metabolites relevant to a specific phenotypic characteristic can be identified. However, the reliability of the analytical data is a prerequisite for correct biological interpretation in metabolomics analysis. In this review the challenges in quantitative metabolomics analysis with regards to analytical as well as data preprocessing steps are discussed. Recommendations are given on how to optimize and validate comprehensive silylation-based methods from sample extraction and derivatization up to data preprocessing and how to perform quality control during metabolomics studies. The current state of method validation and data preprocessing methods used in published literature are discussed and a perspective on the future research necessary to obtain accurate quantitative data from comprehensive GC-MS data is provided

    HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

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    BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

    New Insight into the History of Domesticated Apple: Secondary Contribution of the European Wild Apple to the Genome of Cultivated Varieties

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    The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species

    Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells

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    Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) owing to a reservoir of latently infected cells that contain replication-competent virus1–4. Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8+ lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate virus production, its administration after the depletion of CD8+ lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo. We found viraemia of more than 60 copies per ml in all macaques (n = 14; 100%) and in 41 out of a total of 56 samples (73.2%) that were collected each week after N-803 administration. Notably, concordant results were obtained in ART-treated HIV-infected humanized mice. In addition, we observed that co-culture with CD8+ T cells blocked the in vitro latency-reversing effect of N-803 on primary human CD4+ T cells that were latently infected with HIV. These results advance our understanding of the mechanisms responsible for latency reversal and lentivirus reactivation during ART-suppressed infection
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