Measuring disadvantage in the early years in the UK: A systematic scoping review

Background: The relationship between disadvantage and child health in the early years is well established. For this evidence base to most helpfully inform services, we need to better understand how disadvantage is conceptualised and measured in the literature. We aimed to conceptualise disadvantage measured in child health literature and explore the associations between disadvantage and child health using these measures. Method: We conducted a scoping review using systematic methods to identify key concepts of disadvantage used in empirical child health literature. We searched MEDLINE, Scopus, and grey literature for studies exploring the association between disadvantage and child health outcomes for children aged 0-5 in the United Kingdom. We extracted and analysed data from 86 studies. Results: We developed a framework describing two domains, each with two attributes conceptualising disadvantage: level of disadvantage indicator (individual and area) and content of disadvantage indicator (social and economic). Individual-level measures of disadvantage tended to identify stronger associations between disadvantage and child health compared with area-level measures. Conclusion: The choice of disadvantage indicators, particularly whether individual- or area-level, can affect the inferences made about the relationship between disadvantage and child health. Better access to individual-level disadvantage indicators in administrative data could support development and implementation of interventions aimed at reducing child health inequalities in the early years

Investigating the New Landscapes of Welfare: Housing Policy, Politics and the Emerging Research Agenda

As debates about housing form an increasingly important arena of political controversy, much has been written about the new fissures that have appeared as governments not only struggle to reduce public expenditure deficits but also attempt to address problems such as affordability and homelessness. It is widely anticipated that new conflicts will be played out in the private rental market as access to homeownership becomes unrealistic and the supply of social housing diminishes. However, what other tensions might surface; that hitherto have not been subject to the critical gaze of housing research? In this paper, we provide some thoughts on the nascent policy issues as well as the ideological schisms that are likely to develop in coming years, offering suggestions as to how the focus of housing policy research might be reoriented towards a “politics” framework to capture and better understand the conflicts that are likely to arise

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

The RNA binding protein Cwc2 interacts directly with the U6 snRNA to link the nineteen complex to the spliceosome during pre-mRNA splicing

Intron removal during pre-messenger RNA (pre-mRNA) splicing involves arrangement of snRNAs into conformations that promote the two catalytic steps. The Prp19 complex [nineteen complex (NTC)] can specify U5 and U6 snRNA interactions with pre-mRNA during spliceosome activation. A candidate for linking the NTC to the snRNAs is the NTC protein Cwc2, which contains motifs known to bind RNA, a zinc finger and RNA recognition motif (RRM). In yeast cells mutation of either the zinc finger or RRM destabilize Cwc2 and are lethal. Yeast cells depleted of Cwc2 accumulate pre-mRNA and display reduced levels of U1, U4, U5 and U6 snRNAs. Cwc2 depletion also reduces U4/U6 snRNA complex levels, as found with depletion of other NTC proteins, but without increase in free U4. Purified Cwc2 displays general RNA binding properties and can bind both snRNAs and pre-mRNA in vitro. A Cwc2 RRM fragment alone can bind RNA but with reduced efficiency. Under splicing conditions Cwc2 can associate with U2, U5 and U6 snRNAs, but can only be crosslinked directly to the U6 snRNA. Cwc2 associates with U6 both before and after the first step of splicing. We propose that Cwc2 links the NTC to the spliceosome during pre-mRNA splicing through the U6 snRNA

Structure of the Rna15 RRM–RNA complex reveals the molecular basis of GU specificity in transcriptional 3′-end processing factors

Rna15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3′-end processing factor from Saccharomyces cerevisiae. CFIA is required for polyA site selection/cleavage targeting RNA sequences that surround polyadenylation sites in the 3′-UTR of RNA polymerase-II transcripts. RNA recognition by CFIA is mediated by an RNA recognition motif (RRM) contained in the Rna15 subunit of the complex. We show here that Rna15 has a strong and unexpected preference for GU containing RNAs and reveal the molecular basis for a base selectivity mechanism that accommodates G or U but discriminates against C and A bases. This mode of base selectivity is rather different to that observed in other RRM-RNA structures and is structurally conserved in CstF64, the mammalian counterpart of Rna15. Our observations provide evidence for a highly conserved mechanism of base recognition amongst the 3′-end processing complexes that interact with the U-rich or U/G-rich elements at 3′-end cleavage/polyadenylation sites

"There's nothing”: unemployment, attitudes to work and punitive welfare reform in post-crash Salford

This article explores attitudes and barriers to work and the impact of punitive welfare reform in the city of Salford (Greater Manchester). Contextualising our discussion in relation to the contemporary landscape of inequality and social class in the UK, we draw attention to the trends towards the expansion of low paid work, precarity and stigmatisation, and highlight the need for more qualitative, geographically sensitive, studies of how these phenomena are being played out. Describing the economic context of the City of Salford and the current state of its labour market, we then present the findings from qualitative interviews with a sample of low income, mostly working-class participants, who describe their orientations towards employment, perceptions of the labour market, barriers to employment and interactions with punitive welfare reform. Ultimately, we conclude by noting that both strategies of neoliberal statecraft aimed at the reduction of the charitable state described by Wacquant are at play in Salford and that their result is a discouragement from claiming welfare and a recommodification of labour

Analysis of interactions between ribosomal proteins and RNA structural motifs

<p>Abstract</p> <p>Background</p> <p>One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in <it>T. thermophilus </it>and <it>E. coli</it>, supporting the idea of a core made by both RNA and proteins, conserved by evolution. Recent work showed also that ribosomal RNA is modularly composed. Motifs are generally single-stranded sequences of consecutive nucleotides (ssRNA) with characteristic folding. The role of these motifs in protein-RNA interactions has been so far only sparsely investigated.</p> <p>Results</p> <p>This work explores the role of RNA structural motifs in the interaction of proteins with ribosomal RNA (rRNA). We analyze composition, local geometries and conformation of interface regions involving motifs such as tetraloops, kink turns and single extruded nucleotides. We construct an interaction map of protein binding sites that allows us to identify the common types of shared 3-D physicochemical binding patterns for tetraloops. Furthermore, we investigate the protein binding pockets that accommodate single extruded nucleotides either involved in kink-turns or in arbitrary RNA strands. This analysis reveals a new structural motif, called <it>tripod</it>.</p> <p>It corresponds to small pockets consisting of three aminoacids arranged at the vertices of an almost equilateral triangle. We developed a search procedure for the recognition of tripods, based on an empirical tripod fingerprint.</p> <p>Conclusion</p> <p>A comparative analysis with the overall RNA surface and interfaces shows that contact surfaces involving RNA motifs have distinctive features that may be useful for the recognition and prediction of interactions.</p

Texture variations suppress suprathreshold brightness and colour variations

Discriminating material changes from illumination changes is a key function of early vision. Luminance cues are ambiguous in this regard, but can be disambiguated by co-incident changes in colour and texture. Thus, colour and texture are likely to be given greater prominence than luminance for object segmentation, and better segmentation should in turn produce stronger grouping. We sought to measure the relative strengths of combined luminance, colour and texture contrast using a suprathreshhold, psychophysical grouping task. Stimuli comprised diagonal grids of circular patches bordered by a thin black line and contained combinations of luminance decrements with either violet, red, or texture increments. There were two tasks. In the Separate task the different cues were presented separately in a two-interval design, and participants indicated which interval contained the stronger orientation structure. In the Combined task the cues were combined to produce competing orientation structure in a single image. Participants had to indicate which orientation, and therefore which cue was dominant. Thus we established the relative grouping strength of each cue pair presented separately, and compared this to their relative grouping strength when combined. In this way we observed suprathreshold interactions between cues and were able to assess cue dominance at ecologically relevant signal levels. Participants required significantly more luminance and colour compared to texture contrast in the Combined compared to Separate conditions (contrast ratios differed by about 0.1 log units), showing that suprathreshold texture dominates colour and luminance when the different cues are presented in combination