The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues

Longitudinal Molecular Trajectories of Diffuse Glioma in Adults

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear ¹² . Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of difuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specifc gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at diferent rates across the glioma subtypes, and hypermutation was not associated with diferences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner

Invasion success of a widespread invasive predator may be explained by a high predatory efficacy but may be influenced by pathogen infection

Invasive alien species (IAS) can drive community change through ecological interactions. Parasites and pathogens can play an important role in community function including mitigating or enhancing IAS impacts. Despite this, the degree to which pathogen pressure influences IAS impacts remains poorly understood. We quantified the predatory behaviour of the highly invasive alien harlequin ladybird (Harmonia axyridis) and two UK native species, the 7-spot (Coccinella septempunctata) and 2-spot (Adalia bipunctata) ladybirds, using comparative functional response experiments. We investigated the impacts of pathogen infection on the predatory ability of the ladybirds by exposing individuals to Beauveria bassiana, a widespread entomopathogen. Invasive H. axyridis was a more efficient predator than both the native A. bipunctata and C. septempunctata, often having higher attack and/or lower prey handling time coefficients, whereas native A. bipunctata were the least efficient predators. These differences were found in both adult and larval life-stages. Beauveria bassiana infection significantly altered the predatory efficiency of adult and larval ladybird predators. The effects of pathogenic infection differed between species and life-stage but in many cases infection resulted in a reduced predatory ability. We suggest that the interactions between IAS and pathogens are integral to determining invasion success and impact

Invasion success of a widespread invasive predator may be explained by a high predatory efficacy but may be influenced by pathogen infection

Invasive alien species (IAS) can drive community change through ecological interactions. Parasites and pathogens can play an important role in community function including mitigating or enhancing IAS impacts. Despite this, the degree to which pathogen pressure influences IAS impacts remains poorly understood. We quantified the predatory behaviour of the highly invasive alien harlequin ladybird (Harmonia axyridis) and two UK native species, the 7-spot (Coccinella septempunctata) and 2-spot (Adalia bipunctata) ladybirds, using comparative functional response experiments. We investigated the impacts of pathogen infection on the predatory ability of the ladybirds by exposing individuals to Beauveria bassiana, a widespread entomopathogen. Invasive H. axyridis was a more efficient predator than both the native A. bipunctata and C. septempunctata, often having higher attack and/or lower prey handling time coefficients, whereas native A. bipunctata were the least efficient predators. These differences were found in both adult and larval life-stages. Beauveria bassiana infection significantly altered the predatory efficiency of adult and larval ladybird predators. The effects of pathogenic infection differed between species and life-stage but in many cases infection resulted in a reduced predatory ability. We suggest that the interactions between IAS and pathogens are integral to determining invasion success and impact