This Guide has been written to provide guidance for individuals involved in curriculum design who wish to develop research skills and foster the attributes in medical undergraduates that help develop research. The Guide will provoke debate on an important subject, and although written specifically with undergraduate medical education in mind, we hope that it will be of interest to all those involved with other health professionals' education. Initially, the Guide describes why research skills and its related attributes are important to those pursuing a medical career. It also explores the reasons why research skills and an ethos of research should be instilled into professionals of the future. The Guide also tries to define what these skills and attributes should be for medical students and lays out the case for providing opportunities to develop research expertise in the undergraduate curriculum. Potential methods to encourage the development of research-related attributes are explored as are some suggestions as to how research skills could be taught and assessed within already busy curricula. This publication also discusses the real and potential barriers to developing research skills in undergraduate students, and suggests strategies to overcome or circumvent these. Whilst we anticipate that this Guide will appeal to all levels of expertise in terms of student research, we hope that, through the use of case studies, we will provide practical advice to those currently developing this area within their curriculum.

Corticotropin (ACTH)-releasing factor, vasoactive intestinal peptide, and catecholamines-hormones that stimulate ACTH secretion and cAMP generation-increased cytosolic calcium in AtT-20 cells. The increase in intracellular calcium is presumably a consequence of the stimulated cAMP synthesis, since forskolin, an activator of the catalytic unit of adenylate cyclase, and the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP) also increased the cytosolic levels of this ion. Pretreatment with somatostatin, a neuropeptide that inhibits stimulation of the adenylate cyclase system and the secretion of ACTH blocked the increase of cytosolic calcium. The effect of 8Br-cAMP, which bypasses the cyclase, was not inhibited by somatostatin pretreatment. The source of the increased calcium appears to be mainly extracellular. This is indicated by the inability of the secretagogues to increase cytosolic calcium in a medium deprived of this ion or in the presence of blockers of voltage-gated calcium channels. The involvement of calcium channels in the calcium rise evoked by the secretagogues was supported by experiments using the whole-cell patch-clamp technique. In these experiments 8Br-cAMP increased voltage-dependent calcium currents. These results suggest the following chain of events in the receptor-mediated elevation of cytosolic calcium and the concomitant release of ACTH from hormone-receptor binding --cAMP synthesis --protein kinase activation calcium channel activation -+ increase in cytosolic calcium many steps --ACTH release. Phorbol myristate acetate, a compound which does not stimulate cAMP generation but enhances the release of ACTH in AtT-20 cells, decreased the cytosolic calcium level.The corticotropin (ACTH)-releasing factor (CRF) stimulates the secretion of ACTH and increases the synthesis of cAMP in anterior pituitary cells (1). Extracellular calcium is essential for the stimulation of ACTH release (2). Studies on the involvement of cAMP and calcium in ACTH secretion from the pituitary are hindered by the difficulty of preparing a pure population of ACTH-secreting cells. The mouse pituitary tumor AtT-20 provides a homogeneous corticotrophic cell line that makes such studies more feasible. AtT-20 cells secrete ACTH in response to a variety of secretagogues, some of which, including CRF, vasoactive intestinal peptide (VIP), isoproterenol, and forskolin, increase the levels of cAMP by either a receptor-mediated stimulation of the adenylate cyclase complex or by a direct activation of the catalytic unit (3). The neuropeptide somatostatin blocks the secretagogue-induced increase in cAMP by acting on the GTP-dependent inhibitory protein component (N.) of the adenylate cyclase complex and, consequently, suppresses the release of ACTH induced by secretagogues (3). Removal of calcium from the medium prevents the ACTH release from AtT-20 cells induced by the above secretagogues (3). We now report that the secretagogues that generate cAMP also increase cytosolic calcium and that cAMP analogs incre...

1 The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a model system for the investigation of adenosine 3': 5'-cyclic monophosphate (cyclic AMP)mediated enhancement of calciumevoked adrenocorticotrophin (ACTH) secretion. 2 AtT-20 cells were permeabilized by subjecting the cells to intense electric fields. Exposure of permeabilized cells to calcium (1 mM) in the external medium significantly stimulated ACTH secretion over the first 20 min of exposure. This calcium-stimulated ACTH secretion was dependent upon the presence of MgATP (5 mM 6 The results of the present study support the hypothesis that, in AtT-20 cells, cyclic AMP is acting at some site, distal to calcium entry, which modulates the ability of an increase in cytosolic calcium concentration to stimulate ACTH secretion. One such site may be a GTP-binding protein which the present study suggests may mediate the effects of calcium upon the secretory apparatus. These GTP-binding proteins may be a target for regulation by cyclic AMP.

The 4.1 superfamily of proteins contain a 4.1 ezrin radixin moesin (FERM) domain and are described as linking the cytoskeleton with the plasma membrane. Here, we describe a new FERM domain-containing protein called Willin. Willin has a recognizable FERM domain within its N-terminus and is capable of binding phospholipids. Its intra-cellular distribution can be cytoplasmic or at the plasma membrane where it can co-localize with actin. However, the plasma membrane location of Willin is not influenced by cytochalasin D induced actin disruption but it is induced by the addition of epidermal growth factor.

1 The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a model system for the study of phorbol 12-myristate 13-acetate (PMA)-mediated enhancement of calcium-evoked adrenocorticotrophin (ACTH) secretion. 2 PMA stimulated ACTH secretion from intact cells in a concentration-dependent manner. Other phorbol esters; phorbol 12,13-dibutyrate (PDBu) and phorbol 12,13-didecanoate (PDD) and diacylglycerol analogues; 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG) also stimulated ACTH release from intact AtT-20 cells. This would suggest that activation of protein kinase C (PKC) stimulates ACTH secretion from 3 Calcium stimulated ACTH secretion from electrically-permeabilized cells over the concentration- 6 GTP-y-S (108-1O'-M) stimulated ACTH secretion from permeabilized cells either in the presence or absence of ATP (5 mM) indicating that its effects on secretion are ATP-independent. 7 The results of the present study support the hypothesis that, in AtT-20 cells, PMA is acting at some site distal to calcium entry which modulates the ability of an increase in cytosolic calcium concentration to stimulate ACTH secretion. This site of action is either at the level of or at some stage distal to a GTP-binding protein which mediates the effects of calcium upon secretion. 8 PMA, unlike adenosine 3':5'-cyclic monophosphate (cyclic AMP) (Guild, 1991), can stimulate ACTH secretion from permeabilized cells in the absence of added calcium and guanine nucleotides which suggests that PMA and cyclic AMP are acting through distinct mechanisms at this post calcium site of action.