| 1. |
- Hirst, Catherine, 1989-, et al.
(author)
-
Iron isotopes reveal seasonal variations in the mechanisms for iron-bearing particle and colloid formation in the Lena River catchment, NE Siberia
- 2023
-
In: Geochimica et Cosmochimica Acta. - 0016-7037 .- 1872-9533. ; 363, s. 77-93
-
Journal article (peer-reviewed)abstract
- Large Arctic rivers are an important source of iron (Fe) to the Arctic Ocean, though seasonal variations in the terrestrial source and supply of Fe to the ocean are unknown. To constrain the seasonal variability, we present Fe concentrations and isotopic compositions (δ56Fe) for particulate (>0.22 µm) and colloidal (<0.22 µm–1 kDa) Fe from the Lena River, NE Russia. Samples were collected every month during winter baseflow (September 2012–March 2013) and every 2–3 days before, during and after river ice break-up (May 2015).Iron in particles have isotope ratios lower than crustal values during winter (e.g., δ56FePart = −0.37 ± 0.16‰), and crustal-like values during river ice break-up and spring flood (e.g., δ56FePart = 0.07 ± 0.08‰), indicating a change in the source of particulate Fe between winter and spring flood. Low isotope values are indicative of mineral dissolution, transport of reduced Fe in sub-oxic, ice-covered sub-permafrost groundwaters and near-quantitative precipitation of Fe as particles. Crustal-like isotopic compositions result from the increased supply of detrital particles from riverbank and soil erosion during river ice break-up and flooding. Iron colloids (<0.22 μm) have δ56Fe values that are comparable to or lower than crustal values during winter (e.g., δ56FeCol = −0.08 ± 0.05‰) but similar to or higher than crustal values during spring flood (e.g., δ56FeCol = +0.24 ± 0.11‰). Low δ56Fe ratios for colloidal Fe during winter are consistent with precipitation from isotopically light Fe(II)aq transported in sub-permafrost groundwaters. Higher colloidal δ56Fe ratios during the spring flood indicate that these colloids are supplied from surface soils, where Fe is fractionated via oxidation or organic carbon complexation, similar to during summer. Approximately half of the annual colloidal Fe flux occurs during spring flood while most of the remaining colloidal Fe is supplied during summer months. The total amount of colloidal Fe transported during winter was relatively low. The seasonal variation in colloidal Fe isotope values may be a useful tool to trace the source of colloidal Fe to the Arctic Ocean and monitor future changes in the sources and supply of Fe from the permafrost landscape to the Lena River basin.
|
|
| 2. |
- Machulkin, Aleksei E., et al.
(author)
-
Synthesis and Preclinical Evaluation of Urea-Based Prostate-Specific Membrane Antigen-Targeted Conjugates Labeled with 177Lu
- 2024
-
In: ACS Pharmacology & Translational Science. - : American Chemical Society (ACS). - 2575-9108. ; 7:5, s. 1457-1473
-
Journal article (peer-reviewed)abstract
- 177Lu-labeled small-molecule prostate-specific membrane antigen (PSMA) targeted tracers are therapeutic agents for metastatic castration-resistant prostate cancer. Optimizing molecular design holds the potential to further enhance the pharmacokinetic properties of PSMA-targeted agents while preserving their potent therapeutic effects. In this study, six novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL) urea-based PSMA ligand 2,2′,2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid conjugates were synthesized. These conjugates feature polypeptide linkers containing the Phe-Phe peptide sequence and an aromatic fragment at the ε-NH-Lys group of the DCL fragment. The synthesis yielded products with satisfactory yields ranging from 60% to 72%, paving the way for their preclinical evaluation. The labeling of the new variants of urea-based PSMA inhibitors provided a radiochemical yield of over 95%. The 177Lu-labeled conjugates demonstrated specific and moderate affinity binding to PSMA-expressing human cancer cells PC3-pip in vitro and specific accumulation in PSMA-expressing xenografts in vivo. Based on the results, both the lipophilicity and the type of substituent in the linker significantly influence the binding properties of the PSMA inhibitor and its biodistribution profile. Specifically, the studied variants containing a bromine substituent or a hydroxyl group introduced into the aromatic fragment of the phenylalanyl residue in DCL exhibit higher affinities to PSMA compared to variants with only a chlorine-substituted aromatic fragment or variants without any substituents. The [177Lu]Lu-13C with the bromine substituent was characterized by the highest activity accumulation in blood, salivary glands, muscle, bone, and gastrointestinal tract and had inasmuch as an unfavorable pharmacokinetic profile. The negative charge of the carboxyl group in the phenyl moiety of the [177Lu]Lu-13A variant has demonstrated a positive effect on reducing the retention of activity in the liver and the kidneys (the ratio of tumor to kidneys was 1.3-fold). Low accumulation in normal tissues in vivo indicates that this novel PSMA-targeting inhibitor is a promising radioligand.
|
|
| 3. |
- Trost, Fabian, et al.
(author)
-
Imaging via Correlation of X-Ray Fluorescence Photons
- 2023
-
In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 130:17
-
Journal article (peer-reviewed)abstract
- We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecondduration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.
|
|
