Characterisation of dendritic cell frequency and phenotype in bovine afferent lymph reveals kinetic changes in costimulatory molecule expression.

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, αß 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 naïve host. This should be considered when analysing the response of these cells to vaccines or pathogens.

Late Holocene dietary and cultural variability on the Xingu River, Amazon Basin: A stable isotopic approach.

Although once considered a 'counterfeit paradise', the Amazon Basin is now a region of increasing interest in discussions of pre-colonial tropical land-use and social complexity. Archaeobotany, archaeozoology, remote sensing and palaeoecology have revealed that, by the Late Holocene, populations in different parts of the Amazon Basin were using various domesticated plants, modifying soils, building earthworks, and even forming 'Garden Cities' along the Amazon River and its tributaries. However, there remains a relatively limited understanding as to how diets, environmental management, and social structures varied across this vast area. Here, we apply stable isotope analysis to human remains (n = 4 for collagen, n = 17 for tooth enamel), and associated fauna (n = 61 for collagen, n = 28 for tooth enamel), to directly determine the diets of populations living in the Volta Grande do Rio Xingu, an important region of pre-Columbian cultural interactions, between 390 cal. years BC and 1,675 cal. years AD. Our results highlight an ongoing dietary focus on C3 plants and wild terrestrial fauna and aquatic resources across sites and time periods, with varying integration of C4 plants (i.e. maize). We argue that, when compared to other datasets now available from elsewhere in the Amazon Basin, our study highlights the development of regional adaptations to local watercourses and forest types.

Fossils, fish and tropical forests: prehistoric human adaptations on the island frontiers of Oceania.

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. This article is part of the theme issue 'Tropical forests in the deep human past'.

Human mobility at Tell Atchana (Alalakh), Hatay, Turkey during the 2nd millennium BC: Integration of isotopic and genomic evidence.

The Middle and Late Bronze Age, a period roughly spanning the 2nd 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.

The role of sphingosine-1-phosphate signaling in HSV-1-infected human umbilical vein endothelial cells.

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.

Isotopic and microbotanical insights into Iron Age agricultural reliance in the Central African rainforest.

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.

Isotopic evidence for initial coastal colonization and subsequent diversification in the human occupation of Wallacea.

The resource-poor, isolated islands of Wallacea have been considered a major adaptive obstacle for hominins expanding into Australasia. Archaeological evidence has hinted that coastal adaptations in Homo sapiens enabled rapid island dispersal and settlement; however, there has been no means to directly test this proposition. Here, we apply stable carbon and oxygen isotope analysis to human and faunal tooth enamel from six Late Pleistocene to Holocene archaeological sites across Wallacea. The results demonstrate that the earliest human forager found in the region c. 42,000 years ago made significant use of coastal resources prior to subsequent niche diversification shown for later individuals. We argue that our data provides clear insights into the huge adaptive flexibility of our species, including its ability to specialize in the use of varied environments, particularly in comparison to other hominin species known from Island Southeast Asia.