Background: Potassium isotopic analysis is increasingly performed in both geological and biological contexts as a result of the introduction of MC-ICP-MS instrumentation either equipped with a collision/reaction cell or having the capability of working at "extra -high" mass resolution in order to deal with spectral interference caused by argon hydride (ArH + ) ions. Potassium plays an important role in the central nervous system, and its isotopic analysis could provide an enhanced insight into the corresponding processes, but K isotopic analysis of cerebrospinal fluid is challenging due to the small volume, a few microliter only, typically available. This work aimed at developing a method for determining the K isotopic signature of serum and cerebrospinal fluid at a final K concentration of 25 ng mL -1 using Faraday cup amplifiers equipped with a 10 13 delta lambda resistor. Results: Potassium isotope ratios obtained for reference materials measured at a final K concentration of 25 ng mL -1 were in excellent agreement with the corresponding reference values and the internal and external precision for the delta 41 K value was 0.11 %o (2SE, N = 50) and 0.10 %o (2SD, N = 6), respectively. The robustness against the presence of matrix elements and the concentration mismatch between sample and standard observed at higher K concentrations is preserved at low K concentration. Finally, K isotopic analysis of serum and cerebrospinal fluid (3-12 mu L of sample) of healthy mice of both sexes was performed, revealing a trend towards an isotopically lighter signature for serum and cerebrospinal fluid from female individuals, however being significant for serum only. Significance: This work provides a robust method for high -precision K isotopic analysis at a concentration of 25 ng mL -1 . By monitoring both K isotopes, 39 K and 41 K, with Faraday cups connected to amplifiers with 10 13 Omega resistors, accurate K isotope ratio results are obtained with a two -fold improvement in internal and external precision compared to those obtained with the set-up with traditional 10 11 Omega resistors. The difference in the K isotope ratio in CSF and serum between the sexes, is possibly indicating an influence of the sex or hormones on the fractionation effects accompanying cellular uptake/release.

The strontium (Sr) concentration and Sr-87/Sr-86 isotope ratio have been determined in 132 snow pit samples collected at Dome C, on the East Antarctic Plateau, corresponding to the period 1958-2019, and in 12 surface snow samples collected at the same site in 2016-2017. The average Sr concentration was 8.1 +/- 5.7 pg g(-1) (mean +/- SD) in snow pit samples and 10.1 +/- 8.0 pg g(-1) (mean +/- SD) in surface snow, without any significant temporal trend. The Sr-87/Sr-86 isotope ratio showed small variations (<0.15%), with an average Sr-87/Sr-86 value of 0.7094 +/- 0.0010 (mean +/- SD) in snow pit and 0.7103 +/- 0.0004 (mean +/- SD) in surface snow samples. These results seem to suggest that no change in the source(s) of mineral dust has occurred throughout the period investigated. Comparison of the Sr-87/Sr-86 isotope ratio of the snow samples with those of potential source areas suggests that the mineral dust reaching the East Antarctic plateau over the last decades is of a mixed origin, with a contribution from Patagonia and one or more other source(s) having a more radiogenic Sr isotopic signature, with a major fraction coming from South Australia.

Lead concentration, crustal enrichment factor, and isotope ratios (including those with the less abundant 204Pb) have been measured in PM10 samples collected at Ny-Ålesund (Svalbard Islands) from October 2018 to November 2020, including, for the first time, the autumn and winter seasons. In addition, resuspended soil samples from Svalbard Islands, Iceland, and Alaska were prepared and analysed to provide reference values for local and short-range potential source areas, and back-trajectory analysis was applied to corroborate the findings based on the Pb isotopic signatures.Results showed that the atmospheric Pb concentration reached its maximum in January, progressively decreased until August, remained low until November, and increased again in December. The Pb isotopic composition also showed a clear temporal variation, indicating a shift in the Pb sources with the changing seasons, in agreement with the back-trajectory analysis results. Lead in PM10 samples collected from November to May was entirely (>99%) anthropogenic, and it likely derived from the mining activities in East Kazakhstan and the Altai region, specifically at Leninogorsk (now Ridder). In contrast, the Pb isotopic composition of particulate samples collected from June to October reflected mixed anthropogenic contributions from the North-East USA and Canada, with a significant contribution from natural sources.

Studies on essential trace elements in the context of Alzheimer’s disease (AD) concluded that Cu, Fe and Zn interact with amyloid-β, accelerating plaque formation in the brain. Additionally, Cu and Fe in the vicinity of plaques produce reactive oxygen species (ROS) resulting in oxidative stress, whereas Zn plays a role in the antioxidant defence as a co-factor for antioxidants. In this work, the Cu, Fe and Zn concentrations and isotope ratios were determined in whole blood, blood serum and cerebrospinal fluid of 10 patients diagnosed with AD and 8 control individuals, using tandem (ICP-MS/MS) and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), respectively. In whole blood and blood serum of AD patients, a heavier Cu isotopic composition was observed (significant for whole blood only) compared to controls. Albumin levels in cerebrospinal fluid tend to increase with age, which could indicate an increased leakiness of the blood-brain barrier. In cerebrospinal fluid, a large variability was observed for the Cu and Fe isotope ratios, potentially resulting from that leakiness at the blood-brain barrier. Therefore, potential effects of AD on the concentration and isotopic composition of essential elements in cerebrospinal fluid related to amyloid-β formation could be hidden. Finally, in blood serum, Zn, urea and creatinine concentrations showed an increase with age and showed a significant difference between sexes.

BackgroundPotassium isotopic analysis is increasingly performed in both geological and biological contexts as a result of the introduction of MC-ICP-MS instrumentation equipped with either a collision/reaction cell or having the capability of working at “extra-high” mass resolution in order to deal with spectral interference caused by argon hydride (ArH+) ions. Potassium plays an important role in the central nervous system, and its isotopic analysis could provide an enhanced insight into the corresponding processes, but K isotopic analysis of cerebrospinal fluid is challenging due to the small volume, a few microliter only, typically available. This work aimed at developing a method for determining the K isotopic signature of serum and cerebrospinal fluid at a final K concentration of 25 ng mL-1 using Faraday cup amplifiers equipped with a 1013 Ω resistor.ResultsPotassium isotope ratios obtained for reference materials measured at a final K concentration of 25 ng mL-1 were in excellent agreement with the corresponding reference values and the internal and external precision for the δ41K value were 0.11 ‰ (2SE, N = 50) and 0.10 ‰ (2SD, N = 6), respectively. The robustness against the presence of matrix elements and concentration mismatch between sample and standard observed at higher K concentrations is preserved at low K concentration. Finally, K isotopic analysis of serum and cerebrospinal fluid (3 to 12 μL of sample) of healthy mice of both sexes was performed, revealing a trend towards an isotopically lighter signature for female serum and cerebrospinal fluid, however being significant for serum only.SignificanceThis work provides a robust method for high-precision K isotopic analysis at a concentration of 25 ng mL-1. By monitoring both K isotopes, 39K and 41K, with Faraday cups connected to amplifiers with 1013 Ω resistors, accurate K isotope ratio results are obtained with a two-fold improvement in internal and external precision compared to those obtained with the set-up with traditional 1011 Ω resistors. The difference in the K isotope ratio in CSF and serum between the sexes, is possibly indicating sex-based fractionation effects during cellular uptake/release or might be affected by the hormonal effects.

OBJECTIVES:So far, no 87 Sr/86 Sr mobility studies have been done for Neolithic remains from Belgium and information on the Sr isotopic variability in the region is scarce. This study aims to explore mobility in a Final Neolithic population from the funerary cave 'Grotte de La Faucille', contribute to the understanding of the isotopic composition of bioavailable Sr in Belgium, assess evidence for male mobility using proteomic analysis, and explore possible places of origin for nonlocal individuals.MATERIALS AND METHODS:The 87 Sr/86 Sr isotope ratio of dental enamel from six adults and six juveniles was determined. Liquid chromatography mass spectrometry-based protein analysis was employed to identify individuals of male biological sex. 87 Sr/86 Sr of micromammal teeth, snail shells, and modern plants from three geological areas in Belgium were measured to establish isotopic signatures for bioavailable strontium. Nonlocality was assessed by comparing human 87 Sr/86 Sr isotope ratios to the 87 Sr/86 Sr range for bioavailable Sr.RESULTS:Four individuals yielded 87 Sr/86 Sr isotope ratios consistent with a nonlocal origin. No statistical differences were found between adults and juveniles. Three males were detected in the sample set, of which two show nonlocal 87 Sr/86 Sr values.DISCUSSION:This study provides evidence for mobility in Final Neolithic Belgium. The four nonlocal 87 Sr/86 Sr signatures correspond with the 87 Sr/86 Sr of bio-available Sr in Dutch South Limburg, the Black Forest in Southwest Germany, and regions of France, such as parts of the Paris Basin and the Vosges. The results support the ruling hypothesis of connections with Northern France, brought to light by archeological research.

Alzheimer's' disease (AD) is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary tangles of tau protein in the brain. Aβ plaques are formed by the cleavage of the β-amyloid precursor protein (APP). In addition to protein aggregations, the metabolism of the essential mineral element Cu is also altered during the pathogenesis of AD. The concentration and the natural isotopic composition of Cu were investigated in blood plasma and multiple brain regions (brain stem, cerebellum, cortex, and hippocampus) of young (3-4 weeks) and aged (27-30 weeks) APPNL-G-F knock-in mice and wild-type controls to assess potential alterations associated with ageing and AD. Tandem inductively coupled plasma-mass spectrometry (ICP-MS/MS) was used for elemental analysis and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for high-precision isotopic analysis. The blood plasma Cu concentration was significantly altered in response to both age- and AD-related effects, whereas the blood plasma Cu isotope ratio was only affected by the development of AD. Changes in the Cu isotopic signature of the cerebellum were significantly correlated with the changes observed in blood plasma. The brain stem showed a significant increase in Cu concentration for both young and aged AD transgenic mice compared with healthy controls, whereas the Cu isotopic signature became lighter as a result of age-related changes. In this work, ICP-MS/MS and MC-ICP-MS provided relevant and complementary information on the potential role of Cu in ageing and AD.

The concentration and the isotopic composition of the redox-active essential elements Cu and Fe were investigated in blood plasma and specific brain regions (hippocampus, cortex, brain stem and cerebellum) of mice to assess potential alterations associated with sepsis-associated encephalopathy induced by lipopolysaccharide (LPS) administration. Samples were collected from young (16–22 weeks) and aged (44–65 weeks) mice after intraperitoneal injection of the LPS, an endotoxin inducing neuroinflammation, and from age- and sex-matched controls, injected with phosphate-buffered saline solution. Sector-field single-collector inductively coupled plasma-mass spectrometry was relied upon for elemental analysis and multi-collector inductively coupled plasma-mass spectrometry for isotopic analysis. Significant variations were observed for the Cu concentration and for the Cu and Fe isotope ratios in the blood plasma. Concentrations and isotope ratios of Cu and Fe also varied across the brain tissues. An age- and an inflammatory-related effect was found affecting the isotopic compositions of blood plasma Cu and cerebellum Fe, whereas a regional Cu isotopic redistribution was found within the brain tissues. These findings demonstrate that isotopic analysis of essential mineral elements picks up metabolic changes not revealed by element quantification, making the two approaches complementary.

Potassium isotopic analysis is arousing increasing interest, not only in geochemistry, but also in biomedicine. However, real-life applications are still hindered by the lack of robustness of the methods used. In this work, a novel and robust method for high-precision K isotopic analysis of geological and biological samples was developed, based on the use of a multicollector ICP-mass spectrometer providing a mass resolving power of 15,000 (extra-high resolution mode, XHR). After evaluation of different measurement conditions, i.e., hot vs cold plasma conditions, standard-type vs jet-type sampling cone, and high resolution (HR) vs XHR, a combination of hot plasma conditions, use of the high-transmission jet-type sampling cone, and the XHR mode allowed for high-precision and interference-free K isotopic analysis. Potassium signal monitoring was performed in the ArH+ interference-free 0.006-0.007 amu wide peak shoulder using the XHR mode. The within-run, short-term external, and long-term external precisions for the δ41K value were 0.02‰ (2se, N = 50), 0.03‰ (2SD, N = 7), and 0.06‰ (2SD, N = 163), respectively. A two-stage chromatographic procedure was developed for the isolation of K from both geological and biological samples, and potential matrix effects affecting the K isotope ratio were systematically evaluated. The method was first applied to geological reference materials (RMs) for validation purposes, and the K isotope ratio results were in good agreement with those previously reported. Subsequently, a series of biological RMs, including serum, whole blood, cerebrospinal fluid, bovine muscle, and lobster hepatopancreas, were characterized for their K isotopic composition.