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This study characterized the effect of calorie restriction (CR) on elemental content and stable isotope ratio measurements of bone "collagen" and hair keratin. Adult mice on graded CR (10-40%; 84 days) showed decreased hair δ 15 N, δ 13 C, and δ 34 S values (significantly for δ 15 N) with increasing CR, alongside a significant increase in bone "collagen" δ 15 N values and a decrease in "collagen" δ 13 C values. We propose this was likely due to the intensified mobilization of endogenous proteins, as well as lipids in newly synthesized "collagen". Elemental analysis of bone "collagen" revealed decreased carbon, nitrogen, and sulfur % content with increasing CR which is attributed to a change in the in vivo bone "collagen" structure with extent of CR. This complexity challenges the use of elemental indicators in the assessment of collagen quality in archaeological studies where nutritional stress may be a factor., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Nitrogen isotope ratio analysis (δ15N) of animal tissue is widely used in archaeology and palaeoecology to investigate diet and ecological niche. Data interpretations require an understanding of nitrogen isotope compositions at the base of the food web (baseline δ15N). Significant variation in animal δ15N has been recognised at various spatiotemporal scales and related to changes both in baseline δ15N, linked to environmental and climatic influence on the terrestrial nitrogen cycle, and animal ecology. Isoscapes (models of isotope spatial variation) have proved a useful tool for investigating spatial variability in biogeochemical cycles in present-day marine and terrestrial ecosystems, but so far, their application to palaeo-data has been more limited. Here, we present time-sliced nitrogen isoscapes for late Pleistocene and early Holocene Europe (c. 50,000 to 10,000 years BP) using herbivore collagen δ15N data. This period covers the Last Glacial-Interglacial Transition, during which significant variation in the terrestrial nitrogen cycle occurred. We use generalized linear mixed modelling approaches for interpolation and test models which both include and exclude climate covariate data. Our results show clear changes in spatial gradients of δ15N through time. Prediction of the lowest faunal δ15N values in northern latitudes after, rather than during, the Last Glacial Maximum is consistent with the Late Glacial Nitrogen Excursion (LGNE). We find that including climatic covariate data does not significantly improve model performance. These findings have implications for investigating the drivers of the LGNE, which has been linked to increased landscape moisture and permafrost thaw, and for understanding changing isotopic baselines, which are fundamental for studies investigating diets, niche partitioning, and migration of higher trophic level animals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Reade et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To better comprehend the dietary practices of past populations in the Eastern Baltic region we have created temporally and geographically restricted baselines for the time period of 200-1800 CE. In this multi-isotopic analysis, we report new δ13C, δ15N and δ34S values for 251 faunal bone collagen samples from various archaeological contexts in Estonia representing the most comprehensive set of Iron Age, Medieval and Early Modern Period faunal stable isotope values to date. The results map out the local carbon and nitrogen baselines and define isotopic ranges of local terrestrial, avian and aquatic fauna. We also demonstrate the potential application of sulfur stable isotope analysis in archaeological research. The results demonstrate a clear distinction between δ13C and δ34S values of marine and terrestrial species, however, freshwater fish display notable overlaps with both marine and terrestrial ranges for both δ13C and δ34S values. Herbivores show variation in δ34S values when grouped by region, explained by differences in the local biotopes. This study is the first attempt to connect the Eastern Baltic isotopic baselines and provides more detailed temporal and geographical references to study the local ecologies and interpret the human data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Aguraiuja-Lätti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genetic investigations of Upper Palaeolithic Europe have revealed a complex and transformative history of human population movements and ancestries, with evidence of several instances of genetic change across the European continent in the period following the Last Glacial Maximum (LGM). Concurrent with these genetic shifts, the post-LGM period is characterized by a series of significant climatic changes, population expansions and cultural diversification. Britain lies at the extreme northwest corner of post-LGM expansion and its earliest Late Glacial human occupation remains unclear. Here we present genetic data from Palaeolithic human individuals in the United Kingdom and the oldest human DNA thus far obtained from Britain or Ireland. We determine that a Late Upper Palaeolithic individual from Gough's Cave probably traced all its ancestry to Magdalenian-associated individuals closely related to those from sites such as El Mirón Cave, Spain, and Troisième Caverne in Goyet, Belgium. However, an individual from Kendrick's Cave shows no evidence of having ancestry related to the Gough's Cave individual. Instead, the Kendrick's Cave individual traces its ancestry to groups who expanded across Europe during the Late Glacial and are represented at sites such as Villabruna, Italy. Furthermore, the individuals differ not only in their genetic ancestry profiles but also in their mortuary practices and their diets and ecologies, as evidenced through stable isotope analyses. This finding mirrors patterns of dual genetic ancestry and admixture previously detected in Iberia but may suggest a more drastic genetic turnover in northwestern Europe than in the southwest., (© 2022. The Author(s).)

Kůlna Cave is the only site in Moravia, Czech Republic, from which large assemblages of both Magdalenian and Epimagdalenian archaeological materials have been excavated from relatively secure stratified deposits. The site therefore offers the unrivalled opportunity to explore the relationship between these two archaeological phases. In this study, we undertake radiocarbon, stable isotope (carbon, nitrogen and sulphur), and ZooMS analysis of the archaeological faunal assemblage to explore the chronological and environmental context of the Magdalenian and Epimagdalenian deposits. Our results show that the Magdalenian and Epimagdalenian deposits can be understood as discrete units from one another, dating to the Late Glacial between c. 15,630 cal. BP and 14,610 cal. BP, and c. 14,140 cal. BP and 12,680 cal. BP, respectively. Stable isotope results (δ 13 C, δ 15 N, δ 34 S) indicate that Magdalenian and Epimagdalenian activity at Kůlna Cave occurred in very different environmental settings. Magdalenian occupation took place within a nutrient-poor landscape that was experiencing rapid changes to environmental moisture, potentially linked to permafrost thaw. In contrast, Epimagdalenian occupation occurred in a relatively stable, temperate environment composed of a mosaic of woodland and grassland habitats. The potential chronological gap between the two phases, and their associations with very different environmental conditions, calls into question whether the Epimagdalenian should be seen as a local, gradual development of the Magdalenian. It also raises the question of whether the gap in occupation at Kůlna Cave could represent a change in settlement dynamics and/or behavioural adaptations to changing environmental conditions., Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-020-01254-4., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Central Europe during the Last Glacial Maximum (LGM) was dominated by polar desert and steppe-tundra biomes. Despite this, a human presence during this time period is evident at several locations across the region, including in Switzerland, less than 50 km from the Alpine ice sheet margin. It has been hypothesised that such human activity may have been restricted to brief periods of climatic warming within the LGM, but chronological information from many of these sites are currently too poorly resolved to corroborate this. Here we present a revised chronology of LGM human occupation in Switzerland. AMS radiocarbon dating of cut-marked reindeer (Rangifer tarandus) bones from the sites of Kastelhöhle-Nord and Y-Höhle indicates human occupation of Switzerland was most likely restricted to between 23,400 and 22,800 cal. BP. This timeframe corresponds to Greenland Interstadial 2, a brief warming phase, supporting the hypothesis that human presence was facilitated by favourable climatic episodes. Carbon, nitrogen and sulphur stable isotope analysis of the fauna provides palaeoenvironmental information for this time period. These findings contribute to our understanding of human activity in ice-marginal environments and have implications for understanding cultural connections across central Europe during the LGM.

Rationale: The use of multi-isotopic analysis (δ 15 N, δ 13 C and δ 34 S values) of archaeological bone collagen to assist in the interpretation of diet, movement and mobility of prehistoric populations is gradually increasing, yet many researchers have traditionally avoided investigating sulphur due to its very low concentrations (<0.3%) in mammalian collagen. For this reason, and as a consequence of analytical detection limits, sulphur is usually measured separately from carbon and nitrogen, which leads to longer analytical times and higher costs., Methods: A Thermo Scientific™ EA IsoLink™ isotope ratio mass spectrometry (IRMS) system, with the ability to rapidly heat a gas chromatography (GC) column and concentrate the sample gas online without cryo-trapping, was used at the Radiocarbon Laboratory at the Scottish Universities Environmental Research Centre (SUERC). Optimisation of the GC temperature and carrier gas flow rate in the elemental analyser resulted in improved signal-to-noise (S/N) ratio and sensitivity for SO 2 . This allowed for routine sequential N 2 , CO 2 and SO 2 measurements on small samples of bone collagen., Results: Improvements in sample gas transfer to the mass spectrometer allows for sequential δ 15 N, δ 13 C and δ 34 S values to be measured in 1-1.5 mg samples of bone collagen. Moreover, the sensitivity and S/N ratio of the sample gas, especially SO 2 , is improved, resulting in precisions of ±0.15‰ for δ 15 N values, ±0.1‰ for δ 13 C values and ±0.3‰ for δ 34 S values. Previous instrumentation allowed for the analysis of ~30 unknown samples before undertaking maintenance; however, ~150 unknown samples can now be measured, meaning a 5-fold increase in sample throughput., Conclusions: The ability to sequentially measure δ 15 N, δ 13 C and δ 34 S values rapidly in archaeological bone collagen is an attractive option to researchers who want to build larger, more succinct datasets for their sites of interest, at a much-reduced analytical cost and without destroying larger quantities of archaeological material., (© 2019 John Wiley & Sons, Ltd.)

Objectives: A previous multi-isotope study of archaeological faunal samples from Skútustaðir, an early Viking age settlement on the southern shores of Lake Mývatn in north-east Iceland, demonstrated that there are clear differences in δ(34)S stable isotope values between animals deriving their dietary protein from terrestrial, freshwater, and marine reservoirs. The aim of this study was to use this information to more accurately determine the diet of humans excavated from a nearby late Viking age churchyard., Materials and Methods: δ(13)C, δ(15)N, and δ(34)S analyses were undertaken on terrestrial animal (n = 39) and human (n = 46) bone collagen from Hofstaðir, a high-status Viking-period farmstead ∼10 km north-west of Skútustaðir., Results: δ(34)S values for Hofstaðir herbivores were ∼6‰ higher relative to those from Skútustaðir (δ(34)S: 11.4 ± 2.3‰ versus 5.6 ± 2.8‰), while human δ(13)C, δ(15)N, and δ(34)S values were broad ranging (-20.2‰ to -17.3‰, 7.4‰ to 12.3‰, and 5.5‰ to 14.9‰, respectively)., Discussion: Results suggest that the baseline δ(34)S value for the Mývatn region is higher than previously predicted due to a possible sea-spray effect, but the massive deposition of Tanytarsus gracilentus (midges) (δ(34)S: -3.9‰) in the soil in the immediate vicinity of the lake is potentially lowering this value. Several terrestrial herbivores displayed higher bone collagen δ(34)S values than their contemporaries, suggesting trade and/or movement of animals to the region from coastal areas. Broad ranging δ(13)C, δ(15)N, and δ(34)S values for humans suggest the population were consuming varied diets, while outliers within the dataset could conceivably have been migrants to the area., (© 2016 Wiley Periodicals, Inc.)

An efficient synthesis of 2-substituted O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines from 6-amino-2-mercaptopyrimidin-4-ol has been developed and used to prepare a range of derivatives for evaluation as inhibitors of cyclin-dependent kinase 2 (CDK2). The structure-activity relationships (SARs) are similar to those observed for the corresponding O(6)-cyclohexylmethoxypurine series with the 2-arylsulfonamide and 2-arylcarboxamide derivatives showing excellent potency. Two compounds, 4-(6-amino-4-cyclohexylmethoxy-5-nitrosopyrimidin-2-ylamino)-N-(2-hydroxyethyl)benzenesulfonamide (7q) and 4-(6-amino-4-cyclohexylmethoxy-5-nitrosopyrimidin-2-ylamino)-N-(2,3-dihydroxypropyl)benzenesulfonamide (7s), were the most potent with IC50 values of 0.7 +/- 0.1 and 0.8 +/- 0.0 nM against CDK2, respectively. The SARs determined in this study are discussed with reference to the crystal structure of 4-(6-amino-4-cyclohexylmethoxy-5-nitrosopyrimidin-2-ylamino)-N-(2,3-dihydroxypropyl)benzenesulfonamide (7j) bound to phosphorylated CDK2/cyclin A.

SNAr displacement reactions of 6-cyclohexylmethoxy-2-fluoropurine, 6-amino-2-butylsulfonyl-4-cyclohexylmethoxypyrimidine and 2-amino-6-chloropurine with substituted anilines (e.g. the weakly nucleophilic 4-aminobenzenesulfonamide) are dramaticallyaccelerated in the presence of trifluoroacetic acid and occur especially efficiently in 2,2,2-trifluoroethanol solvent.

A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.