101 research outputs found
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Child poverty transitions: exploring the routes into and out of poverty 2009 to 2012
This study uses data from 2009/2010–2011/2012 to provide new evidence on child poverty transitions since the onset of the recent recession. Its aim is to better understand the patterns of, and drivers behind, moves into and out of poverty for families with children, thereby providing vital new evidence for policy makers tasked with preventing and alleviating child poverty
Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19
Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log-transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population-specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir-associated ALT elevations appear to be multifactorial, and further studies are needed
A healthy start : promoting mental health and well-being in the early primary school years
This study was in part funded by the University of Malta.Mental health problems in children represent a significant international health concern, with up to one in five children using mental health services during the course of any given year. Identifying the processes of what prevents social, emotional and behaviour difficulties (SEBD) and promotes healthy development from an early age can make a significant contribution to the promotion of positive mental health in children. This article describes a longitudinal study which sought to identify the risk and promotive factors as young children move from the early to junior years in primary school. Multilevel analysis was used to identify the individual, classroom, school, home and community factors that predict change in SEBD and in prosocial behaviour in the early school years. It also calculated the cumulative effect of the various risk and promotive factors on the pupils’ well-being and mental health. The article presents the windows of vulnerability and opportunity for young children’s healthy development, proposing a trajectory for healthy development in early and middle childhood.peer-reviewe
Short RNA Guides Cleavage by Eukaryotic RNase III
In eukaryotes, short RNAs guide a variety of enzymatic activities that range from RNA editing to translation repression. It is hypothesized that pre-existing proteins evolved to bind and use guide RNA during evolution. However, the capacity of modern proteins to adopt new RNA guides has never been demonstrated. Here we show that Rnt1p, the yeast orthologue of the bacterial dsRNA-specific RNase III, can bind short RNA transcripts and use them as guides for sequence-specific cleavage. Target cleavage occurred at a constant distance from the Rnt1p binding site, leaving the guide RNA intact for subsequent cleavage. Our results indicate that RNase III may trigger sequence-specific RNA degradation independent of the RNAi machinery, and they open the road for a new generation of precise RNA silencing tools that do not trigger a dsRNA-mediated immune response
Educational Attainment at Age 10–11 Years Predicts Health Risk Behaviors and Injury Risk During Adolescence
Purpose: To examine the effect of educational attainment in primary school on later adolescent
health.
Methods: Education data attainments at age 7 and 11 were linked with (1) primary and secondary
care injury consultation/admissions and (2) the Health Behaviour in School-aged Children survey.
Cox regression was carried out to examine if attainment in primary school predicts time to injury
in adolescence.
Results: Pupils that achieve attainment at age 7 but not at age 11 (i.e., declining attainment over
time in primary school) are more likely to have an injury during adolescence. These children are
also more likely to self-report drinking in adolescence.
Conclusions: Interventions aimed at children with declining attainment in primary school could
help to improve adolescent health
Ability grouping and children’s non-cognitive outcomes
The value of ability grouping is often debated despite being adopted in primary and secondary schools across the UK for the past 80 years. Setting is one form of ability grouping which is widely adopted in English schools; it involves dividing pupils from the same cohort into classes according to ability in a specific subject. While the existing evidence identifies a negative effect on cognitive outcomes, especially for low ability pupils, little research has been undertaken to understand the impact of
setting on non-cognitive outcomes. This paper provides the first evidence of the effect of setting on non-cognitive outcomes when utilising a nationally representative sample of primary-aged pupils and adopting fixed effects and instrumental variables methodologies. For boys, setting in maths negatively impacts non-cognitive outcomes, driven by a worsening of internalising behaviours. No evidence of a significant impact of lowest set placement on non-cognitive outcomes is identified
The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella
Deprived or not deprived? Comparing the measured extent of material deprivation using the UK government's and the Poverty and Social Exclusion surveys' method of calculating material deprivation
Poverty can either be measured directly, through standards of living such as material deprivation, or indirectly through resources available, usually income. Research shows that the optimum measure of poverty combines these methods, a fact that the UK government took cognisance of in its tripartite measure of child poverty. For use in a birth cohort study, two methods of calculating material deprivation were tested: the method used by the UK government taken from the Family Resources Survey (FRS), and the methods used in the Poverty and Social Exclusion (PSE) study at Bristol University. Results show that the former measure, compared to the latter measure, underestimates the depth and extent of material deprivation among families with young children in Scotland
Loss of the yeast SR protein Npl3 alters gene expression due to transcription readthrough
Yeast Npl3 is a highly abundant, nuclear-cytoplasmic shuttling, RNA-binding protein, related to metazoan SR proteins. Reported functions of Npl3 include transcription elongation, splicing and RNA 3' end processing. We used UV crosslinking and analysis of cDNA (CRAC) to map precise RNA binding sites, and strand-specific tiling arrays to look at the effects of loss of Npl3 on all transcripts across the genome. We found that Npl3 binds diverse RNA species, both coding and non-coding, at sites indicative of roles in both early pre-mRNA processing and 3' end formation. Tiling arrays and RNAPII mapping data revealed 3' extended RNAPII-transcribed RNAs in the absence of Npl3, suggesting that defects in pre-mRNA packaging events result in termination readthrough. Transcription readthrough was widespread and frequently resulted in down-regulation of neighboring genes. We conclude that the absence of Npl3 results in widespread 3' extension of transcripts with pervasive effects on gene expression
The CCR4-NOT Complex Physically and Functionally Interacts with TRAMP and the Nuclear Exosome
BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation
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