The degradation of HFR1, a putative bHLH class transcription factor involved in light signaling, is regulated by phosphorylation and requires COP1.

All developmental transitions throughout the life cycle of a plant are influenced by light. In Arabidopsis, multiple photoreceptors including the UV-A/blue-sensing cryptochromes (cry1-2) and the red/far-red responsive phytochromes (phyA-E) monitor the ambient light conditions. Light-regulated protein stability is a major control point of photomorphogenesis. The ubiquitin E3 ligase COP1 (constitutively photomorphogenic 1) regulates the stability of several light-signaling components. HFR1 (long hypocotyl in far-red light) is a putative transcription factor with a bHLH domain acting downstream of both phyA and the cryptochromes. HFR1 is closely related to PIF1, PIF3, and PIF4 (phytochrome interacting factor 1, 3 and 4), but in contrast to the latter three, there is no evidence for a direct interaction between HFR1 and the phytochromes. Here, we show that the protein abundance of HFR1 is tightly controlled by light. HFR1 is an unstable phosphoprotein, particularly in the dark. The proteasome and COP1 are required in vivo to degrade phosphorylated HFR1. In addition, HFR1 can interact with COP1, consistent with the idea of COP1 directly mediating HFR1 degradation. We identify a domain, conserved among several bHLH class proteins involved in light signaling , as a determinant of HFR1 stability. Our physiological experiments indicate that the control of HFR1 protein abundance is important for a normal de-etiolation response.

Levelling up - Securing Health Improvement by Promoting Social Inclusion

Levelling up - Securing Health Improvement by Promoting Social Inclusion - A Cross Border Action Plan for the North West of Ireland  Vision - The aim of 'Levelling Up' is to work towards a society where all voices are heard, where the vulnerable and those on the margins are supported to be involved and in which plans developed for the people are shaped by the people. Their vision is of a region in which organisations and politicians actively demonstrate a commitment to equity – equity both within the North West and between the North West and the rest of Ireland North and South.

Personality Disorder: A Diagnosis for Inclusion - The Northern Ireland Personality Disorder Strategy - The Way Forward - June 2010

Personality Disorder: A Diagnosis for Inclusion - The Northern Ireland Personality Disorder Strategy - The Way Forward - June 2010

Educational pathways of minority youth in Norway: intersections of gender, ethnicity and social class

Educational aspirations during lower secondary school and choice of upper secondary education are important for young people’s future trajectories into higher education and labour market positions. In line with ideas about reflexive, autonomous individuals (Giddens, 1991), choice of education is often represented as a young person’ individual decision, and educational guidance as aimed at discovering what ‘fits’ an individual’s personality, interests and abilities. Educational aspirations and choices are also social patterns that are reproduced. Some population categories represent exceptions from expected patterns of social reproduction of educational level and professions. In several countries, one such category is young people from families with migration experiences (Lauglo, 2000; Modood, 2004). In Norway, students have a legal right to non-compulsory upper secondary schooling and 96 percent of the students continue from lower to upper secondary school. In spite of positive developments regarding minority youths’ completion of upper secondary and higher education in later years, studies still persistently show lower educational attainment among minority youth, particularly among boys (Fekjaer, 2006). However, in lower secondary school, minor ity youth tend to have markedly higher educational aspirations and stronger learning motivation than their majority peers, as well as greater effort in school and strong adherence to school values (Lauglo, 2000) despite lower educational attainment or lower socio-economic backgrounds. In addition, gender differences in educational aspirations seem to be smaller among minority youth. The principal objective of the study in progress that will be presented in this paper, is to describe how processes relating to gendered, ethnic and class-based identities influence young people’s educational choices. The study is undertaken as a PhD project in social anthropology. The methodological approach is ethnographic longitudinal fieldwork in two multicultural lower secondary schools in Oslo. The study is part of a larger project that also include quantitative analyses of longitudinal data covering 9th graders in Oslo 2006 through four data collections during lower and upper secondary school.

Accounting for Big City Growth in Low Paid Occupations: Immigration and/or Service Class Consumption

Growth of 'global cities' in the 1980s was supposed to have involved an occupational polarisation, including growth of low paid service jobs. Though held to be untrue for European cities, at the time, some such growth did emerge in London a decade later than first reported for New York. The question is whether there was simply a delay before London conformed to the global city model, or whether another distinct cause was at work in both cases. This paper proposes that the critical factor in both cases was actually an upsurge of immigration from poor countries providing an elastic supply of cheap labour. This hypothesis and its counterpart based on growth in elite jobs are tested econometrically for the British case with regional data spanning 1975-2008, finding some support for both effects, but with immigration from poor countries as the crucial influence in late 1990s London. Keywords: regional labour markets; wages; employment; international migration; consumer demand JEL Codes: J21, J23, F22, R12

Sex-related and non-sex-related comorbidity subtypes of tic disorders: a latent class approach.

BACKGROUND AND PURPOSE: Recent evidence suggests that there may be more than one Gilles de la Tourette syndrome (GTS)/tic disorder phenotype. However, little is known about the common patterns of these GTS/tic disorder-related comorbidities. In addition, sex-specific phenomenological data of GTS/tic disorder-affected adults are rare. Therefore, this community-based study used latent class analyses (LCA) to investigate sex-related and non-sex-related subtypes of GTS/tic disorders and their most common comorbidities. METHODS: The data were drawn from the PsyCoLaus study (n = 3691), a population-based survey conducted in Lausanne, Switzerland. LCA were performed on the data of 80 subjects manifesting motor/vocal tics during their childhood/adolescence. Comorbid attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depressive, phobia and panic symptoms/syndromes comprised the selected indicators. The resultant classes were characterized by psychosocial correlates. RESULTS: In LCA, four latent classes provided the best fit to the data. We identified two male-related classes. The first class exhibited both ADHD and depression. The second class comprised males with only depression. Class three was a female-related class depicting obsessive thoughts/compulsive acts, phobias and panic attacks. This class manifested high psychosocial impairment. Class four had a balanced sex proportion and comorbid symptoms/syndromes such as phobias and panic attacks. The complementary occurrence of comorbid obsessive thoughts/compulsive acts and ADHD impulsivity was remarkable. CONCLUSIONS: To the best of our knowledge, this is the first study applying LCA to community data of GTS symptoms/tic disorder-affected persons. Our findings support the utility of differentiating GTS/tic disorder subphenotypes on the basis of comorbid syndromes.

Anionic Sites, Fucose Residues and Class I Human Leukocyte Antigen Fate During Interaction of Toxoplasma gondii with Endothelial Cells

Toxoplasma gondii invades and proliferates in human umbilical vein endothelial cells where it resides in a parasitophorous vacuole. In order to analyze which components of the endothelial cell plasma membrane are internalized and become part of the parasitophorous vacuole membrane, the culture of endothelial cells was labeled with cationized ferritin or UEA I lectin or anti Class I human leukocytte antigen (HLA) before or after infection with T. gondii. The results showed no cationized ferritin and UEA I lectin in any parasitophorous vacuole membrane, however, the Class I HLA molecule labeling was observed in some endocytic vacuoles containing parasite until 1 h of interaction with T. gondii. After 24 h parasite-host cell interaction, the labeling was absent on the vacuolar membrane, but presents only in small vesicles near parasitophorous vacuole. These results suggest the anionic site and fucose residues are excluded at the time of parasitophorous vacuole formation while Class I HLA molecules are present only on a minority of Toxoplasma-containig vacuoles.

The Social Inclusion of Older People at Local Level: The Role and Contribution of CDBs

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Social Inclusion of Older People at Local Level:The Role and Contribution of the CDBs - Conference Proceedings

This is a publication of The National Council on Ageing and Older People The Conference took place on October 3, 2005 . It attracted almost 250 delegates from across the statutory, voluntary and private sectors, and from every county. The Conference provided the opportunity for delegates to focus on the issue of social inclusion of older people at local level and the challenges it presents. It also gave us the opportunity to examine the issue in the context of work done at the international and national levels as well as work done at local level. Read the Report (PDF, 317kb)

Loss of single HLA class I allospecificities in melanoma cells due to selective genomic abbreviations.

Expression of human leucocyte antigen (HLA) Class I molecules is essential for the recognition of malignant melanoma (MM) cells by CD8(+) T lymphocytes. A complete or partial loss of HLA Class I molecules is a potent strategy for MM cells to escape from immunosurveillance. In 2 out of 55 melanoma cell cultures we identified a complete phenotypic loss of HLA allospecificities. Both patients have been treated unsuccessfully with HLA-A2 peptides. To identify the reasons underlying the loss of single HLA-A allospecificities, we searched for genomic alterations at the locus for HLA Class I alpha-chain on chromosome 6 in melanoma cell cultures established from 2 selected patients with MM in advanced stage. This deficiency was associated with alterations of HLA-A2 gene sequences as determined by polymerase chain reaction-sequence specific primers (PCR-SSP). Karyotyping revealed a chromosomal loss in Patient 1, whereas melanoma cell cultures established from Patient 2 displayed 2 copies of chromosome 6. Loss of heterozygosity (LOH) using markers located around position 6p21 was detected in both cases. By applying group-specific primer-mixes spanning the 5'-flanking region of the HLA-A2 gene locus the relevant region was amplified by PCR and subsequent sequencing allowed alignment with the known HLA Class I reference sequences. Functional assays using HLA-A2-restricted cytotoxic T-cell clones were performed in HLA-A2 deficient MM cultures and revealed a drastically reduced susceptibility to CTL lysis in HLA-A2 negative cells. We could document the occurrence of selective HLA-A2 deficiencies in cultured advanced-stage melanoma metastases and identify their molecular causes as genomic alterations within the HLA-A gene locus.

Time to Move On from Congregated Settings: A Strategy for Community Inclusion

19.6.2011 I am pleased to present the Report of the Working Group on Congregated Settings, which is the outcome and culmination of a very significant piece of data capture, research and analysis. The Report was initiated by the Primary, Community and Community Care Directorate in 2007 to develop a national plan and associated change programme for moving people from congregated settings to the community in line with Government policy. Click here to download the document

Education of Murine NK Cells Requires Both cis and trans Recognition of MHC Class I Molecules.

Although NK cells use invariant receptors to identify diseased cells, they nevertheless adapt to their environment, including the presence of certain MHC class I (MHC-I) molecules. This NK cell education, which is mediated by inhibitory receptors specific for MHC-I molecules, changes the responsiveness of activating NK cell receptors (licensing) and modifies the repertoire of MHC-I receptors used by NK cells. The fact that certain MHC-I receptors have the unusual capacity to recognize MHC-I molecules expressed by other cells (trans) and by the NK cell itself (cis) has raised the question regarding possible contributions of the two types of interactions to NK cell education. Although the analysis of an MHC-I receptor variant suggested a role for cis interaction for NK cell licensing, adoptive NK cell transfer experiments supported a key role for trans recognition. To reconcile some of these findings, we have analyzed the impact of cell type-specific deletion of an MHC-I molecule and of a novel MHC-I receptor variant on the education of murine NK cells when these mature under steady-state conditions in vivo. We find that MHC-I expression by NK cells (cis) and by T cells (trans), and MHC-I recognition in cis and in trans, are both needed for NK cell licensing. Unexpectedly, modifications of the MHC-I receptor repertoire are chiefly dependent on cis binding, which provides additional support for an essential role for this unconventional type of interaction for NK cell education. These data suggest that two separate functions of MHC-I receptors are needed to adapt NK cells to self-MHC-I.