Visually detected NREM Stage 2 sleep spindles in kindergarten children are associated with current and future emotional and behavioural characteristics

Sleep electroencephalogram spindles are associated with efficient cortical–subcortical connectivity, and intellectual and learning abilities. In the present study, we assessed healthy preschoolers with a twofold aim: (i) to explore associations of non‐rapid eye movement S2 spindles with emotional/behavioural characteristics cross‐sectionally; and (ii) longitudinally. A total of 43 children who were 5 years old underwent objective sleep electroencephalogram monitoring in their homes. Emotional and behavioural dimensions were assessed by parents and teachers with the Strengths & Difficulties Questionnaire at baseline and at follow‐up 1 year later. Non‐rapid eye movement S2 spindles were visually scored and compared with Strengths & Difficulties Questionnaire dimensions. High non‐rapid eye movement S2 spindle density was associated with less internalizing behaviour, more prosocial behaviour and a low total problem score. In girls, high non‐rapid eye movement S2 spindle density was related to low hyperactivity, while in boys it was associated with less internalizing behaviour, more externalizing behaviour and more hyperactivity. Longitudinally, a higher number of non‐rapid eye movement S2 spindles at 5 years old predicted fewer peer problems 12 months later. In kindergarten children, high non‐rapid eye movement S2 spindle density is associated with observable current and future favourable emotional/behavioural patterns. However, gender differences were also found, as should be taken into account in future studies.     

Quality of life for families with spina bifida in Kenya

Spina bifida (SB) affects children worldwide. Studies from developed nations have explored the impact of SB on the quality of life of children and their parents. However, there are no such studies available from developing countries. We have therefore undertaken to document the impact of the disability on the families of affected children in Kenya. A questionnaire was administered to 40 mothers and their children, who were receiving treatment for SB at our institution. The results of this study should indicate where community and governmental resources and educational efforts for the disabled should be directed.     

Erratum to: 'Predictors of outcome in patients with severe aortic stenosis and normal left ventricular function: role of B-type natriuretic peptide' [Eur Heart J 2004;25: 2048-2053]

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Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.     

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.     

Nuclear factor-κB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome

Sustained Toll-like receptor (TLR) stimulation continuously activates antimicrobial genes but paradoxically represses inflammatory genes. This phenomenon, termed TLR tolerance, is essential for preventing fatal inflammatory conditions such as sepsis, but its underlying mechanisms are unclear. We report here that NF-κB binding nucleic acids of gene promoters are tolerogenic motifs, which selectively recruit an NcoR-Hdac3-deacetylated-p50 repressosome to inflammatory genes. Genome-wide analyses of TLR4-induced genes revealed that NF-κB motifs were the only regulatory elements significantly enriched in tolerizable genes. Mutating the NF-κB motifs of tolerizable genes converted them into nontolerizable ones, whereas inserting NF-κB binding motifs into nontolerizable genes conferred the tolerance. Although NF-κB p50 was essential for assembling the repressosome, genetic disruption of the NcoR-Hdac3 interaction alone was sufficient to completely abolish TLR4 tolerance and to render mice vulnerable to sepsis. Thus, the specificity of TLR tolerance is dictated by evolutionally conserved nucleic acid motifs that bound by NF-κB and the NcoR repressosome.