Northern peatland initiation lagged abrupt increases in deglacial atmospheric CH4

Peatlands are a key component of the global carbon cycle. Chronologies of peatland initiation are typically based on compiled basal peat radiocarbon (14C) dates and frequency histograms of binned calibrated age ranges. However, such compilations are problematic because poor quality 14C dates are commonly included and because frequency histograms of binned age ranges introduce chronological artefacts that bias the record of peatland initiation. Using a published compilation of 274 basal 14C dates from Alaska as a case study, we show that nearly half the 14C dates are inappropriate for reconstructing peatland initiation, and that the temporal structure of peatland initiation is sensitive to sampling biases and treatment of calibrated14C dates. We present revised chronologies of peatland initiation for Alaska and the circumpolar Arctic based on summed probability distributions of calibrated 14C dates. These revised chronologies reveal that northern peatland initiation lagged abrupt increases in atmospheric CH4 concentration at the start of the Bølling–Allerød interstadial (Termination 1A) and the end of the Younger Dryas chronozone (Termination 1B), suggesting that northern peatlands were not the primary drivers of the rapid increases in atmospheric CH4. Our results demonstrate that subtle methodological changes in the synthesis of basal 14C ages lead to substantially different interpretations of temporal trends in peatland initiation, with direct implications for the role of peatlands in the global carbon cycle.

Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation

Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer drugs. Here we uncover a role for topoisomerase IIa in RNA polymerase I-directed ribosomal RNA gene transcription, which drives cell growth and proliferation and is upregulated in cancer cells. Our data suggest that topoisomerase IIa is a component of the initiation-competent RNA polymerase Iß complex and interacts directly with RNA polymerase I-associated transcription factor RRN3, which targets the polymerase to promoter-bound SL1 in pre-initiation complex formation. In cells, activation of rDNA transcription is reduced by inhibition or depletion of topoisomerase II, and this is accompanied by reduced transient double-strand DNA cleavage in the rDNA-promoter region and reduced pre-initiation complex formation. We propose that topoisomerase IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.

Secreted Proteins from the Helminth Fasciola hepatica Inhibit the Initiation of Autoreactive T Cell Responses and Prevent Diabetes in the NOD Mouse

Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.

Determinants of breastfeeding initiation in Ireland

BACKGROUND: Ireland continues to rank among countries with the lowest breastfeeding initiation rates. National and regional studies also show that few women in Ireland who initiate exclusive breastfeeding continue to breastfeed for the recommended 6 months.

AIM: To assess the rate of exclusive and partial breastfeeding in Ireland at three time periods: birth to 48 h, 3-4 months following birth, and when the infant was 6-7 months old.

METHODS: A longitudinal national cohort survey of 2527 mothers.

RESULTS: Findings show that just 56 % (n = 1002) of mothers initiated breastfeeding at birth and, at 48 h, 42 % (n = 1064) of women were exclusively breastfeeding their babies. At 6-7 months, only 2.4 % of the 2527 mothers who took part, reported exclusive breastfeeding. Irish women were less likely to initiate breastfeeding (52.6 %) compared with Polish (82.2 %), British (64.5 %), and other nationalities (74.6 %). Multivariate analysis also revealed significant relationships between initiation and socio-economic variables, with mothers' health insurance status being of particular importance.

CONCLUSION: The results highlight the necessity to support the initiation and maintenance of breastfeeding in Ireland, in order to reduce rates of infant morbidity.

Quantitative regulation of FLC via coordinated transcriptional initiation and elongation

The basis of quantitative regulation of gene expression is still poorly understood. In Arabidopsis thaliana, quantitative variation in expression of FLOWERING LOCUS C (FLC) influences the timing of flowering. In ambient temperatures, FLC expression is quantitatively modulated by a chromatin silencing mechanism involving alternative polyadenylation of antisense transcripts. Investigation of this mechanism unexpectedly showed that RNA polymerase II (Pol II) occupancy changes at FLC did not reflect RNA fold changes. Mathematical modeling of these transcriptional dynamics predicted a tight coordination of transcriptional initiation and elongation. This prediction was validated by detailed measurements of total and chromatin-bound FLC intronic RNA, a methodology appropriate for analyzing elongation rate changes in a range of organisms. Transcription initiation was found to vary ∼ 25-fold with elongation rate varying ∼ 8- to 12-fold. Premature sense transcript termination contributed very little to expression differences. This quantitative variation in transcription was coincident with variation in H3K36me3 and H3K4me2 over the FLC gene body. We propose different chromatin states coordinately influence transcriptional initiation and elongation rates and that this coordination is likely to be a general feature of quantitative gene regulation in a chromatin context.

Statin prescription initiation and lifestyle behaviour: a primary care cohort study

BACKGROUND: Statin prescribing and healthy lifestyles contribute to declining cardiovascular disease mortality. Recent guidelines emphasise the importance of giving lifestyle advice in association with prescribing statins but adherence to healthy lifestyle recommendations is sub-optimal. However, little is known about any change in patients' lifestyle behaviours when starting statins or of their recall of receiving advice. This study aimed to examine patients' diet and physical activity (PA) behaviours and their recall of lifestyle advice following initiation of statin prescribing in primary care.

METHOD: In 12 general practices, patients with a recent initial prescription of statin therapy, were invited to participate. Those who agreed received a food diary by post, to record food consumed over 4 consecutive days and return to the researcher. We also telephoned participants to administer brief validated questionnaires to assess typical daily diet (DINE) and PA level (Godin). Using the same methods, food diaries and questionnaires were repeated 3 months later. At both times participants were asked if they had changed their behaviour or received advice about their diet or PA.

RESULTS: Of 384 invited, 122 (32 %) participated; 109 (89.3 %) completed paired datasets; 50 (45.9 %) were male; their mean age was 64 years. 53.2 % (58/109) recalled receiving lifestyle advice. Of those who did, 69.0 % (40/58) reported having changed their diet or PA, compared to 31.4 % (16/51) of those who did not recall receiving advice. Initial mean daily saturated fat intake (12.9 % (SD3.5) of total energy) was higher than recommended; mean fibre intake (13.8 g/day (SD5.5)), fruit/vegetable consumption (2.7 portions/day (SD1.3)) and PA levels (Godin score 7.1 (SD13.9)) were low. Overall, although some individuals showed evidence of behaviour change, there were no significant changes in the proportions who reported high or medium fat intake (42.2 % v 49.5 %), low fibre (51.4 % v 55.0 %), or insufficient PA (80.7 % v 83.5 %) at 3-month follow-up.

CONCLUSION: Whilst approximately half of our cohort recalled receiving lifestyle advice associated with statin prescribing this did not translate into significant changes in diet or PA. Further research is needed to explore gaps between people's knowledge and behaviours and determine how best to provide advice that supports behaviour change.