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Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1) by the pro-inflammatory cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.
Ice-nucleating particle concentrations of the past: insights from a 600-year-old Greenland ice core
(2020)
Ice-nucleating particles (INPs) affect the microphysics in cloud and precipitation processes. Hence, they modulate the radiative properties of clouds. However, atmospheric INP concentrations of the past are basically unknown. Here, we present INP measurements from an ice core in Greenland, which dates back to the year 1370. In total 135 samples were analyzed with the FRIDGE droplet freezing assay in the temperature range from −14 to −35 ∘C. The sampling frequency was set to 1 in 10 years from 1370 to 1960. From 1960 to 1990 the frequency was increased to one sample per year. Additionally, a few special events were probed, including volcanic episodes. The typical time coverage of a sample was on the order of a few months. Historical atmospheric INP concentrations were estimated with a conversion factor, which depends on the snow accumulation rate of the ice core, particle dry deposition velocity, and wet scavenging ratio. Typical atmospheric INP concentrations were on the order of 0.1 L−1 at −25 ∘C. The INP variability was found to be about 1–2 orders of magnitude. Yet, the short-term variability from samples over a seasonal cycle was considerably lower. INP concentrations were significantly correlated to some chemical tracers derived from continuous-flow analysis (CFA) and ion chromatography (IC) over a broad range of nucleation temperatures. The highest correlation coefficients were found for the particle concentration (spherical diameter dp > 1.2 µm). The correlation is higher for a time period of seasonal samples, where INP concentrations follow a clear annual pattern, highlighting the importance of the annual dust input in Greenland from East Asian deserts during spring. Scanning electron microscopy (SEM) analysis of selected samples found mineral dust to be the dominant particle fraction, verifying their significance as INPs. Overall, the concentrations compare reasonably well to present-day INP concentrations, albeit they are on the lower side. However, we found that the INP concentration at medium supercooled temperatures differed before and after 1960. Average INP concentrations at −23, −24, −25, −26, and −28 ∘C were significantly higher (and more variable) in the modern-day period, which could indicate a potential anthropogenic impact, e.g., from land-use change.
Ice nucleating particle concentrations of the past: insights from a
600 year old Greenland ice core
(2020)
Ice nucleating particles (INPs) affect the microphysics in cloud and precipitation processes. Hence, they modulate the radiative properties of clouds. However, atmospheric INP concentrations of the past are basically unknown. Here, we present INP measurements from an ice core in Greenland, which dates back to the year 1370. In total 135 samples were analyzed with the FRIDGE droplet freezing assay in the temperature range from −14 ◦C to −35 ◦C. The sampling frequency was set to 1 in 10 years from 1370 to 1960. From 1960 to 1990 the frequency was increased to 1 sample per year. Additionally, a number of special events were probed, including volcanic episodes. The typical time coverage of a sample was on the order of a few months. Historical atmospheric INP concentrations were estimated with a conversion factor, which depends on the snow accumulation rate of the ice core, particle dry deposition velocity and the wet scavenging ratio. Typical atmospheric INP concentrations were on the order of 0.1 L -1 at −25 ◦C. The INP variability was found to be about 1 – 2 orders of magnitude. Yet, the short-term variability from samples over a seasonal cycle was considerably lower. INP concentrations were significantly correlated to chemical tracers derived from continuous flow analysis (CFA) and ion chromatography (IC) over a broad range of nucleation temperatures. The highest correlation coefficients were found for the particle concentration (dp > 1.2 µm). The correlation is higher for the seasonal samples, where INP concentrations follow a clear annual pattern, highlighting the importance of the annual dust input in Greenland from East Asian deserts during spring. Scanning electron microscopy (SEM) of single particles retrieved from selected samples found particles of soil origin to be the dominant fraction, verifying the significance of mineral dust particles as INPs. Overall, the concentrations compare reasonably well to present day INP concentrations, albeit they are on the lower side. However, we found that the INP concentration at medium supercooled temperatures differed before and after 1960. Average INP concentrations at −23 ◦C, −24 ◦C, −25 ◦C, −26 ◦C and −28 ◦C were significantly higher (and more variable) in the modern day period, which could indicate a potential anthropogenic impact or some post-coring contamination of the topmost, very porous firn.