ALBERT

Description: Subsurface nutrients on the Scotian Shelf, an ocean region at the convergence of the subpolar and subtropical western boundary currents (i.e., Labrador Current and Gulf Stream), are chiefly modulated by upstream shelf and slope waters. Yet little is known about long-term fluctuations in the advective transport of nutrients to the shelf. To examine the relationships between subsurface nutrient concentrations and dominant slope water masses at the Scotian Shelf break, we assembled all available hydrographic data (temperature, salinity) and dissolved nutrient data (nitrate, phosphate, silicate) for the period 1975-2020. Hydrographic and nutrient data were extracted from the Fisheries and Oceans Canada (DFO) data archives MEDS (Marine Environmental Data Section Archive; DFO, 2023a) and BioChem (DFO, 2023b; Devine et al., 2014), respectively, and predominantly include data from current DFO programs (e.g., Atlantic Zone Monitoring Program (AZMP)) and legacy datasets. Hydrographic data consist of vertical water column profiles collected using a conductivity-temperature-depth (CTD) profiler, generally mounted to a rosette sampler equipped with Niskin bottles for discrete water and nutrient sampling (Mitchel et al., 2002). Nutrient (nitrate, phosphate, silicate) measurements generally followed well established colorimetric techniques outlined in detail in the AZMP sampling protocol (Mitchell et al., 2002). Only nutrient data that passed initial quality control (i.e., BioChem quality flags of 1 and 0) are included in the datasets provided here (see Devine et al., 2014 for details on quality control (QC) procedures). In addition to hydrographic and nutrient parameters, datasets further include information on designated regions (e.g., WSS: Western Scotian Shelf, CSS: Central Scotian Shelf, ESS: Eastern Scotian Shelf) as defined in Lehmann et al (2023).

Description: Subsurface nutrients on the Scotian Shelf, an ocean region at the convergence of the subpolar and subtropical western boundary currents (i.e., Labrador Current and Gulf Stream), are chiefly modulated by upstream shelf and slope waters. Yet little is known about long-term fluctuations in the advective transport of nutrients to the shelf. To examine the relationships between subsurface nutrient concentrations and dominant slope water masses at the Scotian Shelf break, we assembled all available hydrographic data (temperature, salinity) and dissolved nutrient data (nitrate, phosphate, silicate) for the period 1975-2020. Hydrographic and nutrient data were extracted from the Fisheries and Oceans Canada (DFO) data archives MEDS (Marine Environmental Data Section Archive; DFO, 2023a) and BioChem (DFO, 2023b; Devine et al., 2014), respectively, and predominantly include data from current DFO programs (e.g., Atlantic Zone Monitoring Program (AZMP)) and legacy datasets. Hydrographic data consist of vertical water column profiles collected using a conductivity-temperature-depth (CTD) profiler, generally mounted to a rosette sampler equipped with Niskin bottles for discrete water and nutrient sampling (Mitchel et al., 2002). Nutrient (nitrate, phosphate, silicate) measurements generally followed well established colorimetric techniques outlined in detail in the AZMP sampling protocol (Mitchell et al., 2002). Only nutrient data that passed initial quality control (i.e., BioChem quality flags of 1 and 0) are included in the datasets provided here (see Devine et al., 2014 for details on quality control (QC) procedures). In addition to hydrographic and nutrient parameters, datasets further include information on designated regions (e.g., WSS: Western Scotian Shelf, CSS: Central Scotian Shelf, ESS: Eastern Scotian Shelf) as defined in Lehmann et al (2023).

Description: Subsurface waters from both hemispheres converge in the Western Equatorial Pacific (WEP), some of which form the Equatorial Undercurrent (EUC) that influences equatorial Pacific productivity across the basin. Measurements of nitrogen (N) and oxygen (O) isotope ratios in nitrate (d15N-NO3 and d18O-NO3), the isotope ratios of dissolved inorganic carbon (d13C-DIC), and complementary biogeochemical tracers reveal that northern and southern WEP waters have distinct biogeochemical histories. Organic matter remineralization plays an important role in setting the nutrient characteristics on both sides of the WEP. However, remineralization in the northern WEP contributes a larger concentration of the nutrients, consistent with the older "age" of northern thermocline- and intermediate-depth waters. Remineralization introduces a relatively low d15N-NO3 to northern waters, suggesting the production of sinking organic matter by N2 fixation at the surface - consistent with the notion that N2 fixation is quantitatively important in the North Pacific. In contrast, remineralization contributes elevated d15N-NO3 to the southern WEP thermocline, which we hypothesize to derive from the vertical flux of high-d15N material at the southern edge of the equatorial upwelling. This signal potentially masks any imprint of N2 fixation from South Pacific waters. The observations further suggest that the intrusion of high d15N-NO3 and d18O-NO3 waters from the eastern margins is more prominent in the northern than southern WEP. Together, these north-south differences enable the examination of the hemispheric inputs to the EUC, which appear to derive predominantly from southern hemisphere waters.

Description: The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.

Description: (1) Background: The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2) Methods: The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3) Results: Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class “HGNET-BCOR” and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 〈 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) Conclusion: IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine.