Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse. However, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer, and viral infection. We uncover an extreme diversity of human neutrophils
in vivo
, reflecting the rates of cell mobilization, differentiation, and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of context-dependent functional responses. In this context, we detected an acute interferon (IFN) response in the blood of HSC-T patients that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.
The offshore Adriatic Basin holds more than 50% of Italian gas reserves together with significant volumes of oil. A number of large and giant‐size biogenic gasfields and medium to large oilfields have been discovered here during the past 60 years. Two petroleum systems have been identified: a Plio‐Pleistocene biogenic gas system, and an Upper Triassic – Lower Jurassic oil system. These systems are described in this paper within a regional geological framework, with particular focus on petroleum system elements (source, reservoir, seal, trap and charge). The biogenic gas play was for several decades the prime focus of Italian E&P efforts throughout the Adriatic area but is now mature, and significant additional discoveries are unlikely to be made without a breakthrough in DHI (direct hydrocarbon indicator) technology. The Mesozoic oil play is as yet unproved in the northern Adriatic area, where large anticlinal structures at depths of up to ca. 6000 m are available for exploration and constitute high‐risk – high‐reward targets. By contrast, the play is proved in the Central and Southern Adriatic where several oilfields are currently producing. Exploration targets still exist here and may generate medium‐sized discoveries although the prevalent heavy‐oil phase may jeopardize their economic value.
Calcite veins and related sulphate-sulphide mineralisation are common in the Buda Hills. Also, abundant hypogenic caves are found along fractures filled with these minerals pointing to the fact that young caveforming fluids migrated along the same fractures as the older mineralising fluids did. The studied vein-filling paragenesis consists of calcite, barite, fluorite and sulphides. The strike of fractures is consistent-NNW-SSEconcluding a latest Early Miocene maximum age for the formation of fracture-filling minerals. Calcite crystals contain coeval primary, hydrocarbon-bearing-and aqueous inclusions indicating that also hydrocarbons have migrated together with the mineralising fluids. Hydrocarbon inclusions are described here for the first time from the Buda Hills. Mixed inclusions, i.e., petroleum with 'water-tail', were also detected, indicating that transcrystalline water migration took place. The coexistence of aqueous and petroleum inclusions permitted to establish the entrapment temperature (80°C) and pressure (85 bar) of the fluid and thus also the thickness of sediments, having been eroded since latest Early Miocene times, was calculated (800 m). Low salinity of the fluids (\1.7 NaCl eq. wt%) implies that hydrocarbon-bearing fluids were diluted by regional karst water. FT-IR investigations revealed that CO 2 and CH 4 are associated with hydrocarbons. Groundwater also contains small amounts of HC and related gases on the basin side even today. Based on the location of the paleo-and recent hydrocarbon indications, identical migration pathways were reconstructed for both systems. Hydrocarbon-bearing fluids are supposed to have migrated north-westward from the basin east to the Buda Hills from the Miocene on.
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