Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks

Magmatic to hydrothermal zircons: Textural and chemical evolution

International audienceZircon is undoubtedly the most sought-after mineral forgeochemical studies, for its ability to provide information onits host rock, spanning from geochronology, tracing of sourceand processes, geothermometry, and, recently, redoxconditions [1]. However, it is crucial to ascertain its primaryorigin, and in the past two decades there has been increasingevidence of its crystallization from hydrothermal fluids [2].Two of the main characteristics that are widely used toascertain the magmatic or hydrothermal origin of zircon aretexture and trace-element chemistry. However, most of thesedata are contradictory and can be similarly attributed to aprimary and secondary origin [3], resulting in a poorunderstanding of hydrothermal zircon characteristics.We present data on a suite of zircons from theAmbohimirahavavy alkaline complex, Madagascar, thatdisplay impressive textural, morphological and compositionalvariations, strongly suggesting a span in origin from magmaticto hydrothermal (Fig. 1). Clearly magmatic zircons yield agesof 20.40 ± 0.16 and 21.21 ± 0.44 Ma. Hydrothermal zirconyields a similar age of 20.64 ± 0.48 Ma. Evidence forhydrothermal origin includes its occurrence with quartz inpseudomorphs after primary minerals, as botryoidal crystalsfilling cavities, and precipitation in exoskarn [4]. Strongvariations in the amounts and distribution of trace element alsooccur among different sectors in zoned crystals

Co-construction of climate services based on a weather stations network: Application in Toulouse agglomeration local authority

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Middle to late Miocene growth of the North Pamir

How and when the Pamir formed remains an open question. This study explores Pamir tectonics recorded in a sedimentary section in the eastern Tajik Basin. A prominent lithofacies change that has been recognized regionally is assigned to the middle Miocene (13.5 Ma based on preferred magnetostratigraphic correlation). Closely following this change, detrital zircon U-Pb age spectra and mudstone bulk-rock Nd values exhibit a sediment source change from the Central to the North Pamir estimated ca. 12 Ma. At the same time, the stable oxygen and carbon isotopic values of carbonate cements show negative and positive shifts, respectively. Combined with previous studies in both the Tajik and Tarim basins, these results suggest that the North Pamir experienced a middle–late Miocene phase of deformation and surface uplift. This supports models proposing middle–late Miocene Pamir tectonism, and climate models implying that coeval Pamir orogenesis deflected Westerly moisture and affected Asian environments

Unravelling granulitic conditions in Early Triassic crustal xenoliths from NE-Qiangtang, Tibet.

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LPS dose-dependently decreases T cell proliferative response to OKT3.

<p>PBMC were primed overnight with LPS concentrations ranging from 0.01 ng/mL to 100 ng/mL (in case of OKT3 stimulation) or from 0.1 ng/mL to 1000 ng/mL (in case of anti-CD2/CD3/CD28-coated beads and PHA stimulations). Then PBMC were stimulated with 4 μg/mL PHA (<b>A</b>), 0.5x10⁶ anti-CD2/CD3/CD28-coated beads/mL (<b>B</b>), or 25 ng/mL OKT3 (<b>C</b>) for 72h. T cell proliferation was measured by flow cytometry and results are expressed as percentages of proliferating cells among total T cells. Each experiment was performed on n = 3 to 4 HV. Technical replicates were summarized by the mean for each individual. For each condition, individual values are summarized on the plots by a horizontal line representing the mean of a given condition.</p

LPS dose-dependent reduction of IFNg secretion by T cells in response to OKT3 stimulation.

<p>PBMC were primed overnight with 1 ng/mL, 10 ng/mL or 100 ng/mL LPS. Then PBMC were stimulated with 25 ng/mL OKT3 for 72h before the surpernatant was recovered for IFNγ measurement. Each experiment was performed on <i>n</i> = 4 HV. Technical replicates were summarized by the mean for each individual. For each condition, individual values are summarized on the plots by a horizontal line representing the mean of a given condition.</p

IFNγ partially restores monocyte accessory cell function.

<p>PBMC were incubated for 12h with medium or 10 ng/mL LPS, washed, and treated with medium or 100 ng/mL IFNγ. MFI of either CD64 (<b>A</b>), HLA-DR (<b>B</b>), CD86 (<b>C</b>) or CD80 (<b>D</b>) on CD14⁺ cells were measured, and MFI ratios calculated by dividing the MFI of treated cells by the MFI of control cells (no treatment). The experiment was performed on <i>n</i> = 4 HV. Technical replicates were summarized by the mean for each individual.</p

IFNγ partially restores T cell proliferative response to OKT3.

<p>PBMC were treated or not overnight with 10 ng/mL LPS, washed and then treated simultaneously or not with 100 ng/mL IFNγ and 25 ng/mL OKT3 for 72 h before T cell proliferation measurement (Black circles: cells primed with LPS and treated with IFNγ+OKT3; open circles: cells primed with LPS and treated with OKT3 but with no IFNγ treatment). T cell proliferation was measured by flow cytometry and results are expressed as percentages of proliferating cells among total T cells. In addition, results are normalized versus proliferation measured after OKT3 stimulation without any LPS priming or IFNγ treatment (control condition). Results are expressed as percentages to the reference proliferative response. The experiments were performed on <i>n</i> = 6 HV. Technical replicates were summarized by the mean for each individual. For each condition, individual values are summarized on the plots by a horizontal line representing the median of a given condition.</p