Grouping practices in the primary school: what influences change?

During the 1990s, there was considerable emphasis on promoting particular kinds of pupil grouping as a means of raising educational standards. This survey of 2000 primary schools explored the extent to which schools had changed their grouping practices in responses to this, the nature of the changes made and the reasons for those changes. Forty eight percent of responding schools reported that they had made no change. Twenty two percent reported changes because of the literacy hour, 2% because of the numeracy hour, 7% because of a combination of these and 21% for other reasons. Important influences on decisions about the types of grouping adopted were related to pupil learning and differentiation, teaching, the implementation of the national literacy strategy, practical issues and school self-evaluation

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

The Spinal Cord Expression of Neuronal and Inducible Nitric Oxide Synthases and Their Contribution in the Maintenance of Neuropathic Pain in Mice

Background: Nitric oxide generated by neuronal (NOS1), inducible (NOS2) or endothelial (NOS3) nitric oxide synthases contributes to pain processing, but the exact role of NOS1 and NOS2 in the maintenance of chronic peripheral neuropathic pain as well as the possible compensatory changes in their expression in the spinal cord of wild type (WT) and NOS knockout (KO) mice at 21 days after total sciatic nerve ligation remains unknown. Methodology/Principal Findings: The mechanical and thermal allodynia as well as thermal hyperalgesia induced by sciatic nerve injury was evaluated in WT, NOS1-KO and NOS2-KO mice from 1 to 21 days after surgery. The mRNA and protein levels of NOS1, NOS2 and NOS3 in the spinal cord of WT and KO mice, at 21 days after surgery, were also assessed. Sciatic nerve injury led to a neuropathic syndrome in WT mice, in contrast to the abolished mechanical allodynia and thermal hyperalgesia as well as the decreased or suppressed thermal allodynia observed in NOS1-KO and NOS2-KO animals, respectively. Sciatic nerve injury also increases the spinal cord expression of NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively. Moreover, the presence of NOS2 is required to increase the spinal cord expression of NOS1 whereas an increased NOS1 expression might avoid the up-regulation of NOS2 in the spinal cord of nerve injured WT mice. Conclusions/Significance: These data suggest that the increased spinal cord expression of NOS1, regulated by NOS2, might be responsible for the maintenance of chronic peripheral neuropathic pain in mice and propose these enzymes as interesting therapeutic targets for their treatment

From father to son: transgenerational effect of tetracycline on sperm viability

The broad-spectrum antibiotic tetracycline is used in animal production, antimicrobial therapy, and for curing arthropods infected with bacterial endosymbionts such as Wolbachia. Tetracycline inhibits mitochondrial translation, and recent evidence indicates that male reproductive traits may be particularly sensitive to this antibiotic. Here, we report the first multi-generation investigation of tetracycline's effects on ejaculate traits. In a study of the pseudoscorpion, Cordylochernes scorpioides, in which siblings were randomly assigned to control and tetracycline treatments across replicate full-sibling families, tetracycline did not affect body size in either sex, female reproduction or sperm number. However, tetracycline-treated males exhibited significantly reduced sperm viability compared to control males, and transmitted this toxic effect of tetracycline on sperm to their untreated sons but not to their F2 grandsons. These results are consistent with tetracycline-induced epigenetic changes in the male germline, and suggest the need for further investigation of transgenerational effects of tetracycline on male reproductive function

Individual and neighborhood-level socioeconomic characteristics in relation to smoking prevalence among black and white adults in the Southeastern United States: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Low individual-level socioeconomic status (SES) is associated with higher prevalence of cigarette smoking. Recent work has examined whether neighborhood-level SES may affect smoking behavior independently from individual-level measures. However, few comparisons of neighborhood-level effects on smoking by race and gender are available.</p> <p>Methods</p> <p>Cross-sectional data from adults age 40-79 enrolled in the Southern Community Cohort Study from 2002-2009 (19, 561 black males; 27, 412 black females; 6, 231 white males; 11, 756 white females) were used in Robust Poisson regression models to estimate prevalence ratios (PRs) and 95% confidence intervals (CI) for current smoking in relation to individual-level SES characteristics obtained via interview and neighborhood-level SES characteristics represented by demographic measures from US Census block groups matched to participant home addresses.</p> <p>Results</p> <p>Several neighborhood-level SES characteristics were modestly associated with increased smoking after adjustment for individual-level factors including lower percentage of adults with a college education and lower percentage of owner-occupied households among blacks but not whites; lower percentage of households with interest, dividends, or net rental income among white males; and lower percentage of employed adults among black females.</p> <p>Conclusions</p> <p>Lower neighborhood-level SES is associated with increased smoking suggesting that cessation programs may benefit from targeting higher-risk neighborhoods as well as individuals.</p

Type III Nrg1 Back Signaling Enhances Functional TRPV1 along Sensory Axons Contributing to Basal and Inflammatory Thermal Pain Sensation

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs) [1]. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons [2]. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions [3]. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K [4], [5], [6], making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function

Socio-economic status is inversely related to bed net use in Gabon

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Large neutral amino acids in the treatment of PKU: from theory to practice

Notwithstanding the success of the traditional dietary phenylalanine restriction treatment in phenylketonuria (PKU), the use of large neutral amino acid (LNAA) supplementation rather than phenylalanine restriction has been suggested. This treatment modality deserves attention as it might improve cognitive outcome and quality of life in patients with PKU. Following various theories about the pathogenesis of cognitive dysfunction in PKU, LNAA supplementation may have multiple treatment targets: a specific reduction in brain phenylalanine concentrations, a reduction in blood (and consequently brain) phenylalanine concentrations, an increase in brain neurotransmitter concentrations, and an increase in brain essential amino acid concentrations. These treatment targets imply different treatment regimes. This review summarizes the treatment targets and the treatment regimens of LNAA supplementation and discusses the differences in LNAA intake between the classical dietary phenylalanine-restricted diet and several LNAA treatment forms

Distinct Kinetics of Memory B-Cell and Plasma-Cell Responses in Peripheral Blood Following a Blood-Stage Plasmodium chabaudi Infection in Mice

B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC). To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD− IgM− CD19+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1)-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25) or secondary (day 10) infection. CD138+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood