Only Children and Cognitive Ability in Childhood: A Cross-Cohort Analysis over 50 Years in the United Kingdom

Only children's uniqueness has intrigued researchers for decades, but many gaps in knowledge remain as to whether only children differ from children who have siblings. We use data from four British birth cohorts (born in 1946, 1958, 1970, 2000–2002) to investigate cross-cohort differences in the composition of only child families and whether the association between being an only child and cognitive ability in childhood has changed over time. Only children show similar scores to children from two child families and higher scores than children with two or more siblings across each of the cohorts analyzed. However, the results also show that—consistent with the finding that, across cohorts, the composition of the only child group has become more associated with social disadvantage—the “only child advantage” has weakened when comparing the most recent birth cohort to the older ones. Adjustment by family sociodemographic characteristics attenuates within and cross-cohort differences. Moreover, the results show that the cognitive advantages associated with being an only child vary considerably by whether the cohort member has been exposed to parental separation or is growing up in a family with lower socioeconomic status. The results highlight diversity in being an only child whose characteristics are conditional on changes throughout time and society

Trypanosomiase humaine africaine : étude d'un score de présomption de diagnostic au Congo

Une enquête cas-témoins a été réalisée au Congo afin de définir une grille de score de présomption de la maladie du sommeil à #T.b. gambiense$, basée sur une sélection de critères cliniques et épidémiologiques de la trypanosomiase, utilisable par les structures sanitaires périphériques. L'enquête a été réalisée sur 163 cas et 326 témoins. Les signes cliniques et les symptômes retenus sont :fièvre, céphalées, prurit et lésions de grattage, diarrhée, oedèmes, adénopathies cervicales, troubles du sommeil, troubles de l'appétit, troubles sexuels, psychisme, signes neurologiques et autres troubles cliniques mineurs. Les autres critères retenus sont les antécédents de trypanosomiase humaine africaine (THA) et l'existence d'un cheptel dans la concession. L'analyse des résultats confirme qu'il n'existe pas de critère ou groupe de critères pathognomoniques. Aucun des critères sélectionnés n'est suffisamment discriminant pour permettre une sélection des trypanosomés parmi les consultants. Une grille de score de présomption semble donc de peu d'utilité au niveau périphérique; ceci est d'autant plus vrai si l'on considère l'augmentation de la charge de travail. Le faible pouvoir discriminant des signes cliniques et des symptômes ainsi que des autres paramètres de la trypanosomiase africaine met en évidence la difficulté de mise en place d'une stratégie d'intégration efficiente en tant qu'outil diagnostique précoce. (Résumé d'auteur

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

Transcript Specificity in Yeast Pre-mRNA Splicing Revealed by Mutations in Core Spliceosomal Components

Appropriate expression of most eukaryotic genes requires the removal of introns from their pre–messenger RNAs (pre-mRNAs), a process catalyzed by the spliceosome. In higher eukaryotes a large family of auxiliary factors known as SR proteins can improve the splicing efficiency of transcripts containing suboptimal splice sites by interacting with distinct sequences present in those pre-mRNAs. The yeast Saccharomyces cerevisiae lacks functional equivalents of most of these factors; thus, it has been unclear whether the spliceosome could effectively distinguish among transcripts. To address this question, we have used a microarray-based approach to examine the effects of mutations in 18 highly conserved core components of the spliceosomal machinery. The kinetic profiles reveal clear differences in the splicing defects of particular pre-mRNA substrates. Most notably, the behaviors of ribosomal protein gene transcripts are generally distinct from other intron-containing transcripts in response to several spliceosomal mutations. However, dramatically different behaviors can be seen for some pairs of transcripts encoding ribosomal protein gene paralogs, suggesting that the spliceosome can readily distinguish between otherwise highly similar pre-mRNAs. The ability of the spliceosome to distinguish among its different substrates may therefore offer an important opportunity for yeast to regulate gene expression in a transcript-dependent fashion. Given the high level of conservation of core spliceosomal components across eukaryotes, we expect that these results will significantly impact our understanding of how regulated splicing is controlled in higher eukaryotes as well

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

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

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

Biomass production of site selective 13C/15N nucleotides using wild type and a transketolase E. coli mutant for labeling RNA for high resolution NMR

Characterization of the structure and dynamics of nucleic acids by NMR benefits significantly from position specifically labeled nucleotides. Here an E. coli strain deficient in the transketolase gene (tktA) and grown on glucose that is labeled at different carbon sites is shown to facilitate cost-effective and large scale production of useful nucleotides. These nucleotides are site specifically labeled in C1′ and C5′ with minimal scrambling within the ribose ring. To demonstrate the utility of this labeling approach, the new site-specific labeled and the uniformly labeled nucleotides were used to synthesize a 36-nt RNA containing the catalytically essential domain 5 (D5) of the brown algae group II intron self-splicing ribozyme. The D5 RNA was used in binding and relaxation studies probed by NMR spectroscopy. Key nucleotides in the D5 RNA that are implicated in binding Mg2+ ions are well resolved. As a result, spectra obtained using selectively labeled nucleotides have higher signal-to-noise ratio compared to those obtained using uniformly labeled nucleotides. Thus, compared to the uniformly 13C/15N-labeled nucleotides, these specifically labeled nucleotides eliminate the extensive 13C–13C coupling within the nitrogenous base and ribose ring, give rise to less crowded and more resolved NMR spectra, and accurate relaxation rates without the need for constant-time or band-selective decoupled NMR experiments. These position selective labeled nucleotides should, therefore, find wide use in NMR analysis of biologically interesting RNA molecules

Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex

<div><p>The RNA exosome complex functions in both the accurate processing and rapid degradation of many classes of RNA. Functional and structural analyses indicate that RNA can either be threaded through the central channel of the exosome or more directly access the active sites of the ribonucleases Rrp44 and Rrp6, but it was unclear how many substrates follow each pathway <i>in vivo</i>. We used CRAC (UV crosslinking and analysis of cDNA) in growing cells to identify transcriptome-wide interactions of RNAs with the major nuclear exosome-cofactor Mtr4 and with individual exosome subunits (Rrp6, Csl4, Rrp41 and Rrp44) along the threaded RNA path. We compared exosome complexes lacking Rrp44 exonuclease activity, carrying a mutation in the Rrp44 S1 RNA-binding domain predicted to disfavor direct access, or with multiple mutations in Rrp41 reported to impede RNA access to the central channel <i>in vitro</i>. Preferential use of channel-threading was seen for mRNAs, 5S rRNA, scR1 (SRP) and aborted tRNAs transcripts. Conversely, pre-tRNAs preferentially accessed Rrp44 directly. Both routes participated in degradation and maturation of RNAPI transcripts, with hand-over during processing. Rrp41 mutations blocked substrate passage through the channel to Rrp44 only for cytoplasmic mRNAs, supporting the predicted widening of the lumen in the Rrp6-associated, nuclear complex. Many exosome substrates exhibited clear preferences for a specific path to Rrp44. Other targets showed redundancy, possibly allowing the efficient handling of highly diverse RNA-protein complexes and RNA structures. Both threading and direct access routes involve the RNA helicase Mtr4. mRNAs that are predominately nuclear or cytoplasmic exosome substrates can be distinguished <i>in vivo</i>.</p></div