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The Camino de Santiago emerged in the first half of the 9th century CE following the reported discovery of the remains of the Apostle St James by the bishop of Iria-Flavia, Teodomiro. Since then, hundreds of thousands of pilgrims have walked from different parts of the Iberian Peninsula, Europe, and further afield to Santiago de Compostela's Cathedral. This route was particularly important to the populations of Navarre and Aragon, two kingdoms in northern Spain that rose to prominence with the resurgence of Christianity from the 11th century onwards. Here, we present multidisciplinary analysis of medieval individuals buried in Navarre and Aragon at a time when the Camino de Santiago was reaching its peak of popularity (11th-15th centuries CE). We use stable isotope analysis (δ15N, δ13C, δ18O, and δ13Cap) and radiocarbon dating to investigate a total of 82 human individuals together with 42 fauna samples from 8 different archaeological sites located in the northeast of the Iberian Peninsula. Twenty of these individuals were buried with a scallop shell, a symbol of a pilgrim who had completed the Camino de Santiago. Our data corroborate the use of the pilgrim's shell since at least the 11th century CE. Moreover, our results suggest that the pilgrimage was mainly an urban phenomenon for populations from the northern Iberian Peninsula, conducted equally by women and men, although with indications that female pilgrims may have had greater access to animal protein than their male counterparts. Our results represent the largest isotopic dataset of medieval individuals linked to the Camino de Santiago, allowing us to further investigate the origins and diets of potential pilgrims and, more generally, other sampled portions of northeastern Iberian society. 1. Introduction 2. Background 2.1. Historical insights into medieval Iberian diets and pilgrims 2.2. Stable isotope analysis and dietary reconstruction 2.3. δ18Oap analysis in tooth enamel 3. Materials and methods 3.1. Materials 3.2. The archaeological sites 3.2.1. Plaza de San José and Plaza del Castillo, Pamplona 3.2.2. Irulegui Castle 3.2.3. Santa María de Arlas, Peralta (14th century CE) 3.2.4. Santa María la Real de Sangüesa (11th-12th centuries CE) 3.2.5. Santa María de Ujué (12th-15th centuries CE) 3.2.6. San Saturnino de Artajona (14th-15th centuries CE) 3.2.7. Jaca, Zaragoza (13th-15th centuries CE) 3.3. Radiocarbon dating 3.4. Stable isotope analysis of bone and dentine collagen, and tooth enamel 3.4.1. δ18Oap and δ13Cap, analysis in tooth enamel 3.4.2. δ13C and δ15N analysis of bone and dentine collagen 3.5. Statistical analysis 4. Results 5. Discussion 5.1. Radiocarbon dating 5.2. Geographical mobility 5.3. Diet and social status 5.4. Medieval pilgrims 5.5. Comparison with data from northern Iberia 6. Conclusions

Oceania is a key region for studying human dispersals, adaptations and interactions with other hominin populations. Although archaeological evidence now reveals occupation of the region by approximately 65–45 000 years ago, its human fossil record, which has the best potential to provide direct insights into ecological adaptations and population relationships, has remained much more elusive. Here, we apply radiocarbon dating and stable isotope approaches to the earliest human remains so far excavated on the islands of Near and Remote Oceania to explore the chronology and diets of the first preserved human individuals to step across these Pacific frontiers. We demonstrate that the oldest human (or indeed hominin) fossil outside of the mainland New Guinea-Aru area dates to approximately 11 800 years ago. Furthermore, although these early sea-faring populations have been associated with a specialized coastal adaptation, we show that Late Pleistocene–Holocene humans living on islands in the Bismarck Archipelago and in Vanuatu display a persistent reliance on interior tropical forest resources. We argue that local tropical habitats, rather than purely coasts or, later, arriving domesticates, should be emphasized in discussions of human diets and cultural practices from the onset of our species' arrival in this part of the world. 1. Introduction 2. Background (a) Human colonization of near and remote Oceania (b) Stable isotope analysis and past human adaptations in the tropics 3. Methods (a) Radiocarbon dating (b) Stable isotope analysis (c) Phytolith analysis of dental calculus 4. Results (a) Radiocarbon dating and Bayesian modelling (b) Stable isotope analysis (c) Phytolith analysis of dental calculus 5. Discussion and conclusion

The Middle and Late Bronze Age, a period roughly spanning the 2(nd) millennium BC (ca. 2000-1200 BC) in the Near East, is frequently referred to as the first 'international age', characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated at Tell Atchana (Alalakh, located in Hatay, Turkey), we explored the role of mobility at the capital of a regional kingdom, named Mukish during the Late Bronze Age, which spanned the Amuq Valley and some areas beyond. We generated strontium and oxygen isotope data from dental enamel for 53 individuals and 77 individuals, respectively, and added ancient DNA data of 10 newly sequenced individuals to a dataset of 27 individuals published in 2020. Additionally, we improved the DNA coverage of one individual from this 2020 dataset. The DNA data revealed a very homogeneous gene pool. This picture of an overwhelmingly local ancestry was consistent with the evidence of local upbringing in most of the individuals indicated by the isotopic data, where only five were found to be non-local. High levels of contact, trade, and exchange of ideas and goods in the Middle and Late Bronze Ages, therefore, seem not to have translated into high levels of individual mobility detectable at Tell Atchana., European Union (EU); Horizon 2020; European Research Council (ERC); Research İnnovation Programme; ERC-2015-StG; FoodTransforms

Tikopia Island, a small and relatively isolated Polynesian Outlier in the Southeast Solomon Islands, supports a remarkably dense human population with minimal external support. Examining long-term trends in human land use on Tikopia through archaeological datasets spanning nearly 3000 years presents an opportunity to investigate pathways to long-term sustainability in a tropical island setting. Here, we trace nutrient dynamics across Tikopia’s three pre-European contact phases (Kiki, Sinapupu, Tuakamali) via stable carbon and nitrogen isotope analysis of commensal Pacific rat (Rattus exulans) and domestic pig (Sus scrofa) bone and tooth dentine collagen. Our results show a decline in δ15N values from the Kiki (c. 800 BC-AD 100) to Sinapupu (c. AD 100–1200) phases, consistent with long-term commensal isotope trends observed on other Polynesian islands. However, increased δ15N coupled with lower δ13C values in the Tuakamali Phase (c. AD 1200–1800) point to a later nutrient rejuvenation, likely tied to dramatic transformations in agriculture and land use at the Sinapupu-Tuakamali transition. This study offers new, quantifiable evidence for deep-time land and resource management decisions on Tikopia and subsequent impacts on island nutrient status and long-term sustainability. 1. Introduction 2. Materials and Methods 2.1. Sample Selection 2.2. Taxonomic Identification via Zooarchaeology by Mass Spectrometry (ZooMS) 2.3. Carbon and Nitrogen Stable Isotope Analysis of Bone and Tooth Dentine Collagen 3. Results

The emergence of agriculture in Central Africa has previously been associated with the migration of Bantu-speaking populations during an anthropogenic or climate-driven ‘opening’ of the rainforest. However, such models are based on assumptions of environmental requirements of key crops (e.g. Pennisetum glaucum) and direct insights into human dietary reliance remain absent. Here, we utilise stable isotope analysis (δ13C, δ15N, δ18O) of human and animal remains and charred food remains, as well as plant microparticles from dental calculus, to assess the importance of incoming crops in the Congo Basin. Our data, spanning the early Iron Age to recent history, reveals variation in the adoption of cereals, with a persistent focus on forest and freshwater resources in some areas. These data provide new dietary evidence and document the longevity of mosaic subsistence strategies in the region., Bleasdale et al. examine the introduction of agricultural crops in the Congo Basin with stable isotope analysis of human and animal remains, charred food remains, and plant microparticles from dental calculus. Their findings reveal variation in the adoption of cereals from the early Iron Age, and provide long-term insights into changing human reliance on different resources.

The Middle and Late Bronze Age Near East, a period roughly spanning the second millennium BC (ca. 2000-1200 BC), is frequently referred to as the first ‘international age’, characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated at Tell Atchana (Alalakh), situated in the northern Levant, we explore the role of mobility at the capital of a regional kingdom. We generated strontium isotope data for 53 individuals, oxygen isotope data for 77 individuals, and added ancient DNA data from 9 new individuals to a recently published dataset of 28 individuals. A dataset like this, from a single site in the Near East, is thus far unparalleled in terms of both its breadth and depth, providing the opportunity to simultaneously obtain an in-depth view of individual mobility and also broader demographic insights into the resident population. The DNA data reveals a very homogeneous gene pool, with only one outlier. This picture of an overwhelmingly local ancestry is consistent with the evidence of local upbringing in most of the individuals indicated by the isotopic data, where only five were found to be ‘non-local’. High levels of contact, trade, and exchange of ideas and goods in the Middle and Late Bronze Ages, therefore, seem not to have translated into high levels of individual mobility detectable at Tell Atchana.

The Iberian Peninsula was at the forefront of the religious, economic, and political changes that swept across Europe during the Medieval Period, including the expansion of Christianity following the disintegration of the Umayyad Caliphate. Between the 9th and the 13th centuries CE, northern Iberia, in particular, witnessed a marked demographic and economic expansion that accompanied the emergence and development of different Christian Kingdoms. A growth in religious infrastructure driven by territorial expansion at the expense of Al-Andalus, and the emerging importance of the Camino de Santiago (the Way of St. James) from the 11th century CE, represented vital processes in changing urban networks and social stratification. However, shifting diets and social structures brought about by these changes require direct study beyond historical texts or localised osteoarchaeological and biomolecular studies in order to determine their wider impacts on peoples’ lived experience. Here, we apply radiocarbon dating (n = 6) and stable carbon and nitrogen isotope analysis to bone and dentine collagen from various locations (n = 10) across the north and north-eastern areas of modern Spain, where three prominent Medieval Christian Kingdoms (Aragon, Castille and Navarre) developed. We sampled 40 human and 32 faunal remains dating to between the 9th and 13th centuries CE, including historical personages such as Sancho Ramirez, Count of Ribagorza and an illegitimate son of King Ramiro I of Aragon; Saint Raymond William or San Ramón de Roda; Pedro de Librana, the first bishop of the city of Zaragoza after its conquest by the Christians in the 12th century CE; an unknown princess from the royal house of Aragon; and individuals from the urban and rural nuclei of Pamplona, Logroño, Lobera de Onsella (Zaragoza), and San Roque de las Quintanillas (Burgos). We compared our results to existing data from the same area demonstrating clear differences in access to animal protein and marine/freshwater resources between rural, urban, and high social status populations on a regional scale. Our data show significant differences in δ15N values between the different groups, with the highest values seen among the ‘elite’, followed by urban populations who benefited from trade and socio-economic diversity. This dataset acts as an important reference point for future studies focusing on changes in the diet and health among different sectors of Medieval society and, in particular, the development of social inequality in the Christian Kingdoms of Iberia as they formed at the centre of novel cultural and religious exchanges across Europe.

The bovine afferent lymphatic cannulation model allows collection of large volumes of afferent lymph and provides an opportunity to study lymphatic cells trafficking from the periphery directly ex-vivo. The technique requires surgical intervention, but influence of the procedure or time post-surgery on cells trafficking in the lymph has not been well documented. Here, we measured the volume of lymph and number of cells/mL collected daily over a two week time-course. Animal to animal variability was demonstrated but no consistent changes in lymph volume or cell density were observed in relation to time post-cannulation. Cell populations (dendritic cells, αβ T-cells, γδ T-cells and NK cells) were analysed by flow cytometry at 1, 3 and 10 days post-cannulation (DPC) and a reduced percentage of γδ T-cells in afferent lymph was observed at 1 DPC. In addition, cell surface molecule expression by afferent lymphatic dendritic cells (ALDC) was assessed due to the key role of these cells in initiating an adaptive immune response. Co-stimulatory molecules CD80 and CD86 were upregulated by CD172a + ve ALDC early in the time-course, suggesting that the cannulation procedure and duration of experiment may impact the activation state of DCs in the naive host. This should be considered when analysing the response of these cells to vaccines or pathogens.

Infections with the herpes simplex virus type 1 (HSV-1) are common and widespread. Most infections remain undetected but severe forms may develop in newborns and in immunocompromised patients. Moreover, HSV-1 might be involved in the pathogenesis of atherosclerosis, which may include viral infection of the endothelium. Antiviral therapy is efficient to treat symptomatic patients. However, an increasing accumulation of resistance-associated mutations has been observed in the viral genome. Thus, new antiviral strategies are focused on host factors. Among others, signaling of bioactive sphingolipids seems to be important in mediating HSV-1 replication. With the present study, regulation and function of sphingosine-1-phosphate (S1P)-based signaling were analyzed in HSV-1-infected human umbilical vein endothelial cells (HUVEC). Our data indicate that viral replication in endothelial cells relies on sphingosine kinase (SK) activity and S1P receptor (S1PR)1,3-5 signaling, which involves the activation of phosphatidylinositol-3-kinase (PI3K) and the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac-1). Inhibitor- or siRNA-meditated reduction of Rac-1 activity decreased HSV-1 replication. In general, targeting S1P-related signaling may be a successful strategy to establish new anti-HSV-1 therapies.