The pathobiology of the septin gene family.

Septins are an evolutionarily conserved group of GTP-binding and filament-forming proteins that belong to the large superclass of P-loop GTPases. While originally discovered in yeast as cell division cycle mutants with cytokinesis defects, they are now known to have diverse cellular roles which include polarity determination, cytoskeletal reorganization, membrane dynamics, vesicle trafficking, and exocytosis. Septin proteins form homo- and hetero-oligomeric polymers which can assemble into higher-order filaments. They are also known to interact with components of the cytoskeleton, ie actin and tubulin. The precise role of GTP binding is not clear but a current model suggests that it is associated with conformational changes which alter binding to other proteins. There are at least 12 human septin genes, and although information on expression patterns is limited, most undergo complex alternative splicing with some degree of tissue specificity. Nevertheless, an increasing body of data implicates the septin family in the pathogenesis of diverse disease states including neoplasia, neurodegenerative conditions, and infections. Here the known biochemical properties of mammalian septins are reviewed in the light of the data from yeast and other model organisms. The data implicating septins in human disease are considered and a model linking these data is proposed. It is posited that septins can act as regulatable scaffolds where the stoichiometry of septin associations, modifications, GTP status, and the interactions with other proteins allow the regulation of key cellular processes including polarity determination. Derangements of such septin scaffolds thus explain the role of septins in disease states. Copyright © 2004 Pathological Society of Great Britain and Ireland.

Guidelines for the psychosocial and bereavement support of family caregivers of palliative care patients

Support for family caregivers, including bereavement follow-up, is a core function of palliative care. Many caregivers acknowledge positive aspects associated with the role; however a considerable proportion will experience poor psychological, social, financial, spiritual, and physical well-being and some will suffer from complicated grief. Many family caregivers have unmet needs and would like more information, preparation, and support to assist them in the caregiving role. There is a shortage of evidence-based strategies to guide health professionals in providing optimal support while the caregiver is providing care and after the patient's death.