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M McKeown

Publications and source records attributed to M McKeown.

At least 19 recordsLinked to original sources
PubMed2003

Gender politics and secure services for women: reflections on a study of staff understandings of challenging behaviour.

This paper discusses the findings of a Q methodological study that investigated the complexity of professional understandings of (attitudes towards) residents in a secure unit for women with learning disabilities and challenging behaviours. Particular attention is afforded to the critical debate regarding women in psychiatric and secure care, including the significant contribution made to this literature by feminist perspectives. A multiprofessional group of staff (n = 38) participated in the study and nine distinct accounts of women's challenging behaviour are described. Despite a considerable amount of recent policy concern with the position of women in psychiatric services, the findings of this research suggest that many front line staff are reluctant to highlight gender in their explanations of women's behaviour. This supports the assertion by Williams et al. (2001), who were involved in the National Gender Training Initiative (NGTI), that most critical theorizing about women's mental health has had minimal impact at the level of individuals' understandings of these important issues. This state of affairs suggests a powerful case for the expansion of staff training as provided in the NGTI, which makes gender central to understanding and emphasizes feminist perspectives.

Female↗
PubMed2001

The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response.

The Drosophila homolog of the retinoid X receptor, ultraspiracle (USP), heterodimerizes with the ecdysone receptor (EcR) to form a functional complex that mediates the effects of the steroid molting hormone ecdysone by activating and repressing expression of ecdysone response genes. As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-modulated manner. We used in vivo, cell culture, and biochemical approaches to analyze the functions of two usp alleles, usp(3) and usp(4), which encode stable proteins with defective DNA-binding domains. We observed that USP is able to activate as well as repress the Z1 isoform of the ecdysone-responsive broad complex (BrC-Z1). Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins. USP3 and USP4 also activate an ecdysone-responsive element, hsp27EcRE, in cultured cells. These results differ from the protein null allele, usp(2), which is unable to mediate activation [Schubiger, M. & Truman, J. W. (2000) Development 127, 1151--1159]. BrC-Z1 repression is compromised in all three usp alleles, suggesting that repression involves the association of USP with DNA. Our results distinguish two mechanisms by which USP modulates the properties of EcR: one that involves the USP DNA-binding domain and one that can be achieved solely through the ligand-binding domain. These newly revealed properties of USP might implicate similar properties for retinoid X receptor.

Alleles↗
PubMed2001

Selection of genomic target RNAs by iterative screening.

A growing number of proteins are known to exert their regulatory or biological functions via RNA binding. In some cases genetic interactions allow us to infer candidate targets for RNA directed regulation, but in many other cases identification of potential regulatory targets is problematic. We have developed an in vitro biochemical screen, SETIS (SElection of < > Target RNAs by Iterative Screening) that allows screening of a major portion of the genome for identification of potential targets for RNA binding proteins.

Animals↗
PubMed2001

Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo.

BACKGROUND: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. RESULTS: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. CONCLUSION: In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.

Amino Acid Sequence↗
PubMed2000

A touch of the blues.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1999

DFak56 is a novel Drosophila melanogaster focal adhesion kinase.

The mammalian focal adhesion kinase (FAK) family of nonreceptor protein-tyrosine kinases have been implicated in controlling a multitude of cellular responses to the engagement of cell surface integrins and G protein-coupled receptors. We describe here a Drosophila melanogaster FAK homologue, DFak56, which maps to band 56D on the right arm of the second chromosome. Full-length DFak56 cDNA encodes a phosphoprotein of 140 kDa, which shares strong sequence similarity not only with mammalian p125(FAK) but also with the more recently described mammalian Pyk2 (also known as CAKbeta, RAFTK, FAK2, and CADTK) FAK family member. DFak56 has intrinsic tyrosine kinase activity and is phosphorylated on tyrosine in vivo. As is the case for FAK, tyrosine phosphorylation of DFak56 is increased upon plating Drosophila embryo cells on extracellular matrix proteins. In situ hybridization and immunofluorescence staining analysis showed that DFak56 is ubiquitously expressed with particularly high levels within the developing central nervous system. We utilized the UAS-GAL4 expression system to express DFak56 and analyze its function in vivo. Overexpression of DFak56 in the wing imaginal disc results in wing blistering in adults, a phenotype also observed with both position-specific integrin loss of function and position-specific integrin overexpression. Our results imply a role for DFak56 in adhesion-dependent signaling pathways in vivo during D. melanogaster development.

Amino Acid Sequence↗
PubMed1999

Isolation and characterization of Dek, a Drosophila eph receptor protein tyrosine kinase.

We have isolated a Drosophila receptor protein tyrosine kinase (RTK) of the Eph subfamily. Dek, for Drosophila Eph kinase, possesses all the domains characteristic of the Eph subfamily of RTKs and is equally similar in sequence to both the EphA and the EphB subclasses. Antibody staining and promoter fusions to axon-targeted reporters reveal that Dek is expressed by a large subset of developing embryonic interneurons and is targeted to their axons and growth cones at the time of axon pathfinding. Dek is also expressed by photoreceptor cells of third-instar larvae as they project axons into the optic brain lobe. Misexpression and overexpression of full-length Dek or kinase-inactive Dek do not grossly affect axon pathfinding.

Animals↗
PubMed1999

SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development.

The Drosophila ecdysone receptor (EcR)/ultraspiracle (USP) heterodimer is a key regulator in molting and metamorphoric processes, activating and repressing transcription in a sequence-specific manner. Here, we report the isolation of an EcR-interacting protein, SMRTER, which is structurally divergent but functionally similar to the vertebrate nuclear corepressors SMRT and N-CoR. SMRTER mediates repression by interacting with Sin3A, a repressor known to form a complex with the histone deacetylase Rpd3/HDAC. Importantly, we identify an EcR mutant allele that fails to bind SMRTER and is characterized by developmental defects and lethality. Together, these results reveal a novel nuclear receptor cofactor that exhibits evolutionary conservation in the mechanism to achieve repression and demonstrate the essential role of repression in hormone signaling.

Amino Acid Sequence↗
PubMed1999

Passivity vs. militancy: a Q methodological study of nurses' industrial relations on Merseyside (England).

This paper describes a Q methodological study of accounts of nurses' industrial relations expressed by a sample of nurses (n = 60) drawn from the geographical area of Merseyside, United Kingdom (UK). The participants completed a 65-item Q sort made up of statements which could be ranked in terms of their relevance to an understanding of their industrial relations situation. Of interest was the importance of the narrative accounts which nurses draw upon in making sense of their employment relations, having the potential to underpin or delimit their actions. The notion of industrial action was an important focus of this research. Q methodology was chosen to allow the meaningful investigation of such subjectivity, with interesting tensions between differing notions of professionalism and militancy apparent from the analysis. Six accounts of industrial relations, which are available to be drawn on by nurses, are described and interpreted within a social constructionist framework. Some implications for the conduct of nurses' industrial relations in the UK are contemplated.

England↗
PubMed1999

Q methodology, risk training and quality management.

The results of a Q methodological study of professional understandings of the notion of risk in mental health services within the UK are discussed in relation to the relevance for staff training and quality assurance. The study attempted to access the diversity of understandings of risk issues amongst a multi-professional group of staff (n = 60) attending inter-agency risk training workshops in 1998. Q methodology is presented as both an appropriate means for such inquiry and as a novel experiential technique for training purposes. A tentative argument is advanced that the qualitative accounts generated by Q research could assist in systematic reviews of quality, complementing the singularly quantitative approaches typically represented in the audit process.

Attitude of Health Personnel↗
PubMed1999

Race, psychopathy and the self: a discourse analytic study.

This discourse analytic study explores the implicit psychological models articulated within the admission reports of black and white men admitted to a forensic hospital under the diagnostic category of psychopathy. The white admission reports reproduce a traditional psychological model of the self in which intra-psychic states are causally linked to external behaviour whilst the black reports de-emphasize internal states and stress the relevance of the external world in influencing psychological equilibrium. The influence of these models upon the experience of psychopathology is discussed and it is argued that they are directly relevant to the (seemingly) paradoxical underepresentation of black men under the medico-legal category of psychopathy.

Black or African American↗
PubMed1998

pcdr, a novel gene with sexually dimorphic expression in the pigment cells of the Drosophila eye.

We report the molecular cloning and characterization of pcdr (pigment cell dehydrogenase reductase), a Drosophila visual system-specific gene with novel properties of spatial, temporal and sexual regulation. Short chain dehydrogenase/reductases are a family of proteins that catalyze mechanistically conserved dehydrogenase/reductase reactions in a wide range of cells and tissues. These enzymes are required in a variety of reactions ranging from steroid metabolism and prostaglandin synthesis to alcohol detoxification. The Drosophila pcdr gene encodes a new member of this family, displaying 42% amino acid sequence identity to the mammalian prostaglandin dehydrogenase. pcdr expression is restricted to the visual system with very high levels found in the pigment cells. Interestingly, expression of pcdr mRNA is sexually dimorphic with males showing higher levels of expression than females. This sexual dimorphism is under the control of the sex differentiation cascade as transformer and transformer 2 mutations shift females to a male-like level of expression. Finally, we demonstrate that a region of 335 nucleotides including sequences upstream and just downstream of the transcription start is sufficient to reproduce the normal expression pattern.

Amino Acid Sequence↗
PubMed1998

Dissatisfaction encodes a tailless-like nuclear receptor expressed in a subset of CNS neurons controlling Drosophila sexual behavior.

The dissatisfaction (dsf) gene is necessary for appropriate sexual behavior and sex-specific neural development in both sexes. dsf males are bisexual and mate poorly, while mutant females resist male courtship and fail to lay eggs. Males and females have sex-specific neural abnormalities. We have cloned dsf and rescued both behavioral and neural phenotypes. dsf encodes a nuclear receptor closely related to the vertebrate Tailless proteins and is expressed in both sexes in an extremely limited set of neurons in regions of the brain potentially involved in sexual behavior. Expression of a female transformer cDNA under the control of a dsf enhancer in males leads to dsf-like bisexual behavior.

Amino Acid Sequence↗
PubMed1998

Time for action: a new system for training mental health practitioners.

Continuing the debate from previous issues of Mental Health Care, MICK McKEOWN and colleagues call for a radical rethink in mental health training. Institutionalised neglect continues on hospital wards and in the community. The answer is a systematic approach to mental health care. Training should focus on psychosocial interventions which are known to be effective. It should take place in the work setting, to ensure developments are integrated into the routine practice of all members of the mental health team.

Clinical Competence↗
PubMed1997

dissatisfaction, a gene involved in sex-specific behavior and neural development of Drosophila melanogaster.

Few mutations link well defined behaviors with individual neurons and the activity of specific genes. In Drosophila, recent evidence indicates the presence of a doublesex-independent pathway controlling sexual behavior and neuronal differentiation. We have identified a gene, dissatisfaction (dsf), that affects sex-specific courtship behaviors and neural differentiation in both sexes without an associated general behavioral debilitation. Male and female mutant animals exhibit abnormalities in courtship behaviors, suggesting a requirement for dsf in the brain. Virgin dsf females resist males during courtship and copulation and fail to lay mature eggs. dsf males actively court and attempt copulation with both mature males and females but are slow to copulate because of maladroit abdominal curling. Structural abnormalities in specific neurons indicate a role for dsf in the differentiation of sex-specific abdominal neurons. The egg-laying defect in females correlates with the absence of motor neuronal innervation on uterine muscles, and the reduced abdominal curling in males correlates with alteration in motor neuronal innervation of male ventral abdominal muscles. Epistasis experiments show that dsf acts in a tra-dependent and dsx-independent manner, placing dsf in the dsx-independent portion of the sex determination cascade.

Abdomen↗
PubMed1997

A role for ultraspiracle, the Drosophila RXR, in morphogenetic furrow movement and photoreceptor cluster formation.

Many of the same genes needed for proper eye and limb development in vertebrates, such as hairy, hedgehog, patched and cyclic AMP-dependent protein kinase A, are responsible for patterning Drosophila imaginal discs, the tissues that will give rise to the adult cuticle structures. This is well demonstrated in the control of morphogenetic furrow movement and differentiation in the eye imaginal disc. We report that ultraspiracle, the gene encoding the Drosophila cognate of the Retinoid X Receptor, is required for normal morphogenetic furrow movement and ommatidial cluster formation. Examination of the expression of genes involved in regulating the furrow suggests that ultraspiracle defines a novel regulatory pathway in eye differentiation.

Animals↗
PubMed1996

Understanding the needs of relatives of patients within a special hospital for mentally disordered offenders: a basis for improved services.

This paper outlines one component of a major research study, which will form the basis for a new service for relatives of schizophrenia sufferers within a special hospital. The aim of this initial component has been twofold: firstly to identify and understand the needs of relatives in terms of their present knowledge and understanding of schizophrenia; and secondly to establish what stress the relatives are presently experiencing in maintaining contact with patients and whether this stress may have an impact on the management of schizophrenia at the hospital. A purposive sample of 17 relatives were interviewed using two semi-structured interview protocols. All interviews were audio-taped and later transcribed for analysis. The data have provided an illuminating insight into the thoughts and feelings of relatives and indicate many ways in which a service for relatives could be tailored. It is apparent that many relatives are currently not being supported, involved or allowed to contribute to the care of their family member at Ashworth Hospital. This present situation is stressful for relatives and is likely to have a detrimental effect on the course of schizophrenia in patients at Ashworth Hospital.

Family↗