Exchangeability of mammalian DNA ligases between base excision repair pathways

In mammalian cells, DNA ligase IIIalpha and DNA ligase I participate in the short- and long-patch base excision repair pathways, respectively. Using an in vitro repair assay employing DNA ligase-depleted cell extracts and DNA substrates containing a single lesion repaired either through short-patch (regular abasic site) or long-patch (reduced abasic site) base excision repair pathways, we addressed the question whether DNA ligases are specific to each pathway or if they are exchangeable. We find that immunodepletion of DNA ligase I did not affect the short-patch repair pathway but blocked long-patch repair, suggesting that DNA ligase IIIa is not able to substitute DNA ligase I during long-patch repair. In contrast, immunodepletion of DNA ligase IIIa did not significantly affect either pathway. Moreover, repair of normal abasic sites in wild-type and X-ray cross-complementing gene 1 (XRCC1)-DNA ligase IIIalpha-immunodepleted cell extracts involved similar proportions of short- and long-patch repair events. This suggests that DNA ligase I was able to efficiently substitute the XRCC1-DNA ligase IIIa complex during short-patch repair.

The gut microbiota in obesity and metabolic disease - a novel therapeutic target

Obesity is sweeping the westernized world at a rate which far outstrips human genomic evolution, highlighting the importance of the obesogenic environment. Diet is an important component of this obesogenic environment, with certain diets (high fat, high refined carbohydrates and sugar) predisposing to overweight. On the other hand, there are also foods shown to protect against obesity and the diseases of obesity, including whole plant foods, dairy products, dietary fibre and functional foods like probiotics, prebiotics and phytochemicals. Interestingly, many of these foods mediate their health-promoting activities through the gut microbiota. The human gut microbiota itself has recently been identified as a contributory factor in this obesogenic environment, with differences observed between lean and obese. Evidence from human studies indicates that important groups of fermentative bacteria differ in abundance between lean and obese. Recently it has been suggested that anomalous microbiota composition in infancy can predispose to overweight in later life, highlighting the important role of optimal microbiota successional development, and that – as observed in laboratory animals – the gut microbiota may contribute to the aetiology of obesity. In this review we will introduce the gut microbiota, describe its interactions with major dietary components and the host, and then go on to discuss evidence indicating that the gut microbiota may contribute to the obesogenic environment. Finally, we will explore possible strategies for modulating the composition and activity of the human gut microbiota which may impact on obesity or the metabolic diseases associated with obesity. (Nutritional Therapy & Metabolism 2009; 27: 113-33)

Prediction of moisture, calorific value, ash and carbon content of two dedicated bioenergy crops using near-infrared spectroscopy

The potential of near infrared spectroscopy in conjunction with partial least squares regression to predict Miscanthus xgiganteus and short rotation coppice willow quality indices was examined. Moisture, calorific value, ash and carbon content were predicted with a root mean square error of cross validation of 0.90% (R2 = 0.99), 0.13 MJ/kg (R2 = 0.99), 0.42% (R2 = 0.58), and 0.57% (R2 = 0.88), respectively. The moisture and calorific value prediction models had excellent accuracy while the carbon and ash models were fair and poor, respectively. The results indicate that near infrared spectroscopy has the potential to predict quality indices of dedicated energy crops, however the models must be further validated on a wider range of samples prior to implementation. The utilization of such models would assist in the optimal use of the feedstock based on its biomass properties.

Stable isotopes and diet: their contribution to Romano-British research

The study of stable isotopes surviving in human bone is fast becoming a standard response in the analysis of cemeteries. Reviewing the state of the art for Roman Britain, the author shows clear indications of a change in diet (for the better) following the Romanisation of Iron Age Britain—including more seafood, and more nutritional variety in the towns. While samples from the bones report an average of diet over the years leading up to an individual's death, carbon and nitrogen isotope signatures taken from the teeth may have a biographical element—capturing those childhood dinners. In this way migrants have been detected—as in the likely presence of Africans in Roman York. While not unexpected, these results show the increasing power of stable isotopes to comment on populations subject to demographic pressures of every kind.

Self-organized 40Hz synchronization in a physiological theory of EEG

We present evidence that large-scale spatial coherence of 40 Hz oscillations can emerge dynamically in a cortical mean field theory. The simulated synchronization time scale is about 150 ms, which compares well with experimental data on large-scale integration during cognitive tasks. The same model has previously provided consistent descriptions of the human EEG at rest, with tranquilizers, under anesthesia, and during anesthetic-induced epileptic seizures. The emergence of coherent gamma band activity is brought about by changing just one physiological parameter until cortex becomes marginally unstable for a small range of wavelengths. This suggests for future study a model of dynamic computation at the edge of cortical stability.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.