Climatic significance of the marginalization of Scots pine (Pinus sylvestris L.) c. 2500 BC at White Moss, south Cheshire, UK

Subfossil wood from White Moss, south Cheshire, has become the focus of palaeoenvironmental research employing not only conventional coring, pollen analysis, radiocarbon dating and dendrochronology on pine and oak, but also the exhumation of in situ peat areas and dendroecology of the pine ring-width records. Initial dendrochronological research at the site yielded five pine chronologies dating from 3520 to 2462 cal. BC. These and other data indicate three episodes of pine colonization of the mire in the period between 3643 and 1740 cal. BC. Comparison of the pollen and spore records suggest that pine became marginalized at the site c. 2500 cal. BC after successive episodes of increased wetness, and this may represent a staged response to climatic deterioration. Two oak chronologies were dated by reference to the Belfast and to English oak master chronologies to 3228-2898 BC and 2190-1891 BC, respectively, showing the possible co-existence of pine and oak on the mire for part of the time. Further dendrochronological work on subfossil pine at the site resulted in a chronology (WM4) that was cross-matched with pine from elsewhere in England, and subsequently dated absolutely to 2881-2559 BC. Detailed dendroecological information, such as fire episodes and periods of environmental stress indicated in the tree-ring records, have been assigned, precisely and accurately, to calendar years in prehistory. The detailed data show the potential for both dendroecological and wider palaeoclimatic and palaeoenvironmental information that may become available from prehistoric bog-pine chronologies, which might then permit precise correlation and comparisons of proxy-climate data between sites

Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation

Epithelial cells develop morphologically characteristic apical domains that are bordered by tight junctions, the apical-lateral border. Cdc42 and its effector complex Par6-atypical protein kinase c (aPKC) regulate multiple steps during epithelial differentiation, but the mechanisms that mediate process-specific activation of Cdc42 to drive apical morphogenesis and activate the transition from junction formation to apical differentiation are poorly understood. Using a small interfering RNA screen, we identify Dbl3 as a guanine nucleotide exchange factor that is recruited by ezrin to the apical membrane, that is enriched at a marginal zone apical to tight junctions, and that drives spatially restricted Cdc42 activation, promoting apical differentiation. Dbl3 depletion did not affect junction formation but did affect epithelial morphogenesis and brush border formation. Conversely, expression of active Dbl3 drove process-specific activation of the Par6-aPKC pathway, stimulating the transition from junction formation to apical differentiation and domain expansion, as well as the positioning of tight junctions. Thus, Dbl3 drives Cdc42 signaling at the apical margin to regulate morphogenesis, apical-lateral border positioning, and apical differentiation

High-resolution sub-cellular imaging by correlative NanoSIMS and electron microscopy of amiodarone internalisation by lung macrophages as evidence for drug-induced phospholipidosis

Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level and reveals its accumulation within the lysosomes, providing direct evidence for amiodarone-induced phospholipidosis. Chemical fixation using tannic acid effectively seals cellular membranes aiding intracellular retention of diffusible drugs