Bidirectional transport between the trans-Golgi network and the endosomal system

The exchange of proteins and lipids between the trans-Golgi network (TGN) and the endosomal system requires multiple cellular machines, whose activities are coordinated in space and time to generate pleomorphic, tubulo-vesicular carriers that deliver their content to their target compartments. These machines and their associated protein networks are recruited and/or activated on specific membrane domains where they select proteins and lipids into carriers, contribute to deform/elongate and partition membrane domains using the mechanical forces generated by actin polymerization or movement along microtubules. The coordinated action of these protein networks contributes to regulate the dynamic state of multiple receptors recycling between the cell surface, endosomes and the TGN, to maintain cell homeostasis as exemplified by the biogenesis of lysosomes and related organelles, and to establish/maintain cell polarity. The dynamic assembly and disassembly of these protein networks mediating the exchange of membrane domains between the TGN and endosomes regulates cell-cell signalling and thus the development of multi-cellular organisms. Somatic mutations in single network components lead to changes in transport dynamics that may contribute to pathological modifications underlying several human diseases such as mental retardation.

The sedimentology and diagenesis of the Pendleside limestone group in the Craven Basin of Northern England. Available in 2 volumes.

This thesis describes the stratigraphy, sedimentology and diagenesis of the Pendleside Limestone (Asbian age), a sequence of limestones, shales and dolostones in the Clitheroe area of N. W. England. Field study of 19 measured sections indicates that it was deposited in a rhythmically subsiding basin (Craven Basin) because of movements on the Mid-Craven Fault which was active in Dinantian times. The sequence is up to 190m thick and consists mostly of distal turbidite deposits which have been reworked at horizons when sediment accumulation built up to the wave base. The original depositional fabric and mineralogy of the Pendleside Limestone Group has been extensively modified by diagenetic processes including cementation, authi­genesis, dolomitization and silicification. These processes have been studied using a wide variety of laboratory techniques. The carbonate cements of the PendIeside Limestone consist predominantly of ferroan calcite and non-ferroan calcite with microdolomite incIusions. The former is probably a stable replacement of original-high-magnesian calcite. Cementation was accompanied by the formation of authigenic albite and quartz. Much of the upper part of the Pendleside Limestone has been extensively dolomitized and chertified. Several distinct zones of dolomitization are found which increase in thickness and intensity towards the top of the Pendleside Limestone Group. The dolostone horizons correspond to coarser-grained lithologies deposited during periods of shallow water sedimentation. The composition of the dolomites changes from ferroan dolomite in the lower part of the Group to non-ferroan dolomite in the upper part. The low strontium and sodium content of the dolostones in association with the other evidence suggests that the dolomitization was brought about in an open system by the mixing of marine and fresh water in phreatic lens which were established at periodic intervals. The dolomitization was closely associated with chertification although this was initiated by the dissolution of siliceous spicules which provided the necessary source of silica.

Directing migration of endothelial progenitor cells with applied DC electric fields

Naturally-occurring, endogenous electric fields (EFs) have been detected at skin wounds, damaged tissue sites and vasculature. Applied EFs guide migration of many types of cells, including endothelial cells to migrate directionally. Homing of endothelial progenitor cells (EPCs) to an injury site is important for repair of vasculature and also for angiogenesis. However, it has not been reported whether EPCs respond to applied EFs. Aiming to explore the possibility to use electric stimulation to regulate the progenitor cells and angiogenesis, we tested the effects of direct-current (DC) EFs on EPCs. We first used immunofluorescence to confirm the expression of endothelial progenitor markers in three lines of EPCs. We then cultured the progenitor cells in EFs. Using time-lapse video microscopy, we demonstrated that an applied DC EF directs migration of the EPCs toward the cathode. The progenitor cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signaling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs are an effective signal that guides EPC migration through VEGF receptor signaling in vitro. Applied EFs may be used to control behaviors of EPCs in tissue engineering, in homing of EPCs to wounds and to an injury site in the vasculature.