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.

Chronic child abuse and domestic violence: Children and families with long-term and complex needs

It is estimated that up to one million children may have been exposed to domestic violence in the UK, with significant consequences for their social and emotional development in childhood and later life. At a time when the central and devolved administrations in the UK have developed strategies to tackle domestic violence, this paper reports the findings from a study conducted on children in the child protection system with long-term and complex needs as a result of experiencing domestic violence. The research identifies the characteristics of the children and their families and tracks their careers through the child protection system. The findings indicate that professionals have an awareness of domestic violence, and that younger children with younger parents are most likely to experience prolonged periods in the child protection system. Domestic violence in this context typically co-exists in families experiencing other difficulties such as substance misuse and socio-economic deprivation. In conclusion, the paper argues that Government policy and professional practice should primarily be concerned with assessing the risk that men present, rather than the risk that children are at. By reframing professional interventions, men are more likely to be challenged to accept responsibility for their behaviour and the consequences for their families.

AINT/ERIC/TACC: an expanding family of proteins with C-terminal coiled coil domains:an expanding family of proteins with C-terminal coiled coil domains

The AINT/ERIC/TACC genes encode novel proteins with a coiled coil domain at their C-terminus. The founding member of this expanding family of genes, transforming acidic coiled coil 1 (TACC1), was isolated from a BAC contig spanning the breast cancer amplicon-1 on 8p11. Transfection of cells in vitro with TACC1 resulted in anchorage-independent growth consistent with a more "neoplastic" phenotype. Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains. TACC2, located at 10q26, is similar to anti-zuai-1 (AZU-1), a candidate breast tumour suppressor gene, and ECTACC, an endothelial cell TACC which is upregulated by erythropoietin (Epo). The murine homologue of TACC3, murine erythropoietin-induced cDNA (mERIC-1) was also found to be upregulated by Epo in the Friend virus anaemia (FVA) model by differential display-PCR. Human ERIC-1, located at 4p16.3, has been cloned and encodes an 838-amino acid protein whose N- and C-terminal regions are highly homologous to the shorter 558-amino acid murine protein, mERIC-1. In contrast, the central portions of these proteins differ markedly. The murine protein contains four 24 amino acid imperfect repeats. ARNT interacting protein (AINT), a protein expressed during embryonic development in the mouse, binds through its coiled coil region to the aryl hydrocarbon nuclear translocator protein (ARNT) and has a central portion that contains seven of the 24 amino acid repeats found in mERIC-1. Thus mERIC-1 and AINT appear to be developmentally regulated alternative transcripts of the gene. Most members of the TACC family discovered so far contain a novel nine amino acid putative phosphorylation site with the pattern [R/K]-X(3)-[E]-X(3)-Y. Genes with sequence homology to the AINT/ERIC/TACC family in other species include maskin in Xenopus, D-TACC in Drosophila and TACC4 in the rabbit. Maskin contains a peptide sequence conserved among eIF-4E binding proteins that is involved in oocyte development. D-TACC cooperates with another conserved microtubule-associated protein Msps to stabilise spindle poles during cell division. The diversity of function already attributed to this protein family, including both transforming and tumour suppressor properties, should ensure that a new and interesting narrative is about to unfold.

Working with a child Exposed to Community and Domestic violence in Northern Ireland: An Illustrated Case Example.

The focus of this paper is on the author’s multi-modal therapeutic practice with a 7-year-old boy referred to the Family Trauma Centre, following paramilitary assaults on his father. The work also addresses the boy’s experience of domestic violence. The work is contextualised in terms of the ‘Peace Process’ in Northern Ireland, including the establishment of the Family Trauma Centre as a response to the needs of victims of the Troubles. A rationale for working with children using a multi-modal approach is presented.

Family support, social capital, resilience and adolescent coping

All too often young people are excluded in practice from the general policy and professional consensus that partnership and participation should underpin work with children, young people and their families. If working with troubled and troublesome young people is to be based on family support, it will require not only the clear statement of that policy but also demonstration that it can be applied in practice. Achieving that involves setting out a plausible theory of change that can be rigorously evaluated. This paper suggests a conceptual model that draws on social support theory to harness the ideas of social capital and resilience in a way that can link formal family support interventions to adolescent coping. Research with young people attending three community-based projects for marginalized youth is used to illustrate how validated tools can be used to measure and document the detail of support, resilience, social capital and coping in young people's lives. It is also suggested that there is sufficient fit between the findings emerging from the study and the model to justify the model being more rigorously tested.

Home curation versus teenage photography: Photo displays in the family home

In this paper we report an empirical study of the photographic portrayal of family members at home. Adopting a social psychological approach and focusing oil intergenerational power dynamics, our research explores the use of domestic photo displays in family representation. Parents and their teenagers from eight families in the south of England were interviewed at home about their interpretations of both stored and displayed photos within the home. Discussions centred on particular photographs found by the participants to portray self and family in different ways. The findings show that public displays of digital photos are still curated by mothers of the households, but with more difficulty and less control all with analogue photos. In addition, teenagers both contribute and comply with this curation within the home, whilst at the same time developing additional ways of presenting their families and themselves online that are 'unsupervised' by the curator. We highlight the conflict of interest that is at play within teen and parent practices and consider the challenges that this presents for supporting the representation of family through the design of photo display technology. (C) 2009 Elsevier Ltd. All rights reserved.

Systemic Family Therapy for Families who have Experienced Trauma: A Randomised Controlled Trial

This paper describes a randomised controlled trial (RCT) investigation of the added value of systemic family therapy (SFT) over individually focused cognitive behavioural therapy (CBT) for families in which one or more members has suffered trauma and been referred to a community-based psychotherapy centre. The results illustrate how an apparently robust design can be confounded by high attrition rates, low average number of therapeutic sessions and poor protocol adherence. The paper highlights a number of general and specific lessons regarding the resources and processes involved that can act as a model for those planning to undertake studies of this type and scope. A key message is that the challenges of conducting RCTs in ‘real world’ settings should not be underestimated. The wider implications in relation to the place of RCTs within the creation of the evidence base for complex psycho-social interventions is discussed and the current movement towards a phased mixed-methods approach, including the appropriate use of RCTs, which some might argue is a return to the original vision of evidence-based practice (EBP), is affirmed.

Political Violence and Child Adjustment in Northern Ireland: Testing Pathways in a Social-Ecological Model Including Single- and Two-Parent Families

Moving beyond simply documenting that political violence negatively impacts children, we tested a social ecological hypothesis for relations between political violence and child outcomes. Participants were 700 mother child (M = 12.1 years, SD = 1.8) dyads from 18 working-class, socially deprived areas in Belfast, Northern Ireland, including single- and two-parent families. Sectarian community violence was associated with elevated family conflict and children's reduced security about multiple aspects of their social environment (i.e., family, parent child relations, and community), with links to child adjustment problems and reductions in prosocial behavior. By comparison, and consistent with expectations, links with negative family processes, child regulatory problems, and child outcomes were less consistent for nonsectarian community violence. Support was found for a social ecological model for relations between political violence and child outcomes among both single- and two-parent families, with evidence that emotional security and adjustment problems were more negatively affected in single-parent families. The implications for understanding social ecologies of political violence and children's functioning are discussed.

Testing a social ecological model for relations between political violence and child adjustment in Northern Ireland

Relations between political violence and child adjustment are matters of international concern. Past research demonstrates the significance of community, family, and child psychological processes in child adjustment, supporting study of interrelations between multiple social ecological factors and child adjustment in contexts of political violence. Testing a social ecological model, 300 mothers and their children (M = 12.28 years, SD = 1.77) from Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland, completed measures or community discord, family relations, and children's regulatory processes (i.e., emotional security) and outcomes. Historical political violence in neighborhoods based on objective records (i.e., politically motivated deaths) were related to family members' reports of current sectarian antisocial behavior and nonsectarian antisocial behavior. Interparental conflict and parental monitoring and children's emotional security about both the community and family contributed to explanatory pathways for relations between sectarian antisocial behavior in communities and children's adjustment problems. The discussion evaluates support for social ecological models for relations between political violence and child adjustment and its implications for understanding relations in other parts of the world.

Nostalgically Man dwells on this Earth: Objects and domestic space in The Royal Tenenbaums and The Darjeeling Ltd

The films of Wes Anderson feature a peculiar attention to the representation of dwellings in relation to narrative development, filmic style and characters' identities. As is true of clothing, in Anderson's cinema homes with their architecture, furniture and objects strongly contribute to a nostalgic dislocation of the characters from contemporary time. Considering the house as the prime locus of identity and the core of the patriarchal family, the family home is often depicted by Anderson as the last physical trace left by the absent father; a utopian place that the characters aim to rebuild or to recall through its objectification. This paper aims to analyse the (re)construction of the family home in The Royal Tenenbaums, and will investigate its absence and surrogates in The Darjeeling Ltd.

The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea.

Background

G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum.

Results

Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification.

Conclusions

Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.

Work-family characteristics as determinants of sickness absence: A large-scale cohort study of three occupational grades

This study examined the previously unexplored occupational grade-specific relationships of domestic responsibilities, the age of children, and work-family spillover, with registered sickness absence (>3 days' sick leave episodes, a mean follow-up of 17 months; n = 18,366 municipal employees; 76% women). The results showed that negative spillover from work into family life predicted a heightened rate of sickness absence spells among both women and men in all occupational categories (except upper white-collar men), but especially among blue-collar and lower white-collar employees. Furthermore, among all white-collar employees (except upper white-collar men), having young children (

Political Violence and Child Adjustment: Longitudinal Tests of Sectarian Antisocial Behavior, Family Conflict, and Insecurity as Explanatory Pathways

Understanding the impact of political violence on child maladjustment is a matter of international concern. Recent research has advanced a social ecological explanation for relations between political violence and child adjustment. However, conclusions are qualified by the lack of longitudinal tests. Toward examining pathways longitudinally, mothers and their adolescents (M = 12.33, SD = 1.78, at Time 1) from 2-parent families in Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland, completed measures assessing multiple levels of a social ecological model. Utilizing autoregressive controls, a 3-wave longitudinal model test (T1, n = 299; T2, n = 248; T3, n = 197) supported a specific pathway linking sectarian community violence, family conflict, childrens insecurity about family relationships, and adjustment problems.

Discrete Conditional Phase-type model (DC_Ph) for patient waiting time with a logistic regression component to predict patient admission to hospital

Discrete Conditional Phase-type (DC-Ph) models are a family of models which represent skewed survival data conditioned on specific inter-related discrete variables. The survival data is modeled using a Coxian phase-type distribution which is associated with the inter-related variables using a range of possible data mining approaches such as Bayesian networks (BNs), the Naïve Bayes Classification method and classification regression trees. This paper utilizes the Discrete Conditional Phase-type model (DC-Ph) to explore the modeling of patient waiting times in an Accident and Emergency Department of a UK hospital. The resulting DC-Ph model takes on the form of the Coxian phase-type distribution conditioned on the outcome of a logistic regression model.