Influence of elastase on alanine-rich peptide hydrogels

The self-assembly of the alanine-rich amphiphilic peptides Lys(Ala)6Lys (KA6K) and Lys(Ala)6Glu (KA6E)with homotelechelic or heterotelechelic charged termini respectively has been investigated in aqueous solution. These peptides contain hexa-alanine sequences designed to serve as substrates for the enzyme elastase. Electrostatic repulsion of the lysine termini in KA6K prevents self-assembly, whereas in contrast KA6E is observed, through electron microscopy, to form tape-like fibrils, which based on X-ray scattering contain layers of thickness equal to the molecular length. The alanine residues enable efficient packing of the side-chains in a beta-sheet structure, as revealed by circular dichroism, FTIR and X-ray diffraction experiments. In buffer, KA6E is able to form hydrogels at sufficiently high concentration. These were used as substrates for elastase, and enzyme-induced de-gelation was observed due to the disruption of the beta-sheet fibrillar network. We propose that hydrogels of the simple designed amphiphilic peptide KA6E may serve as model substrates for elastase and this could ultimately lead to applications in biomedicine and regenerative medicine.

'Hey little rich boy, take a good look at me': punk, class and British oi!

This article looks at the controversial music genre Oi! in relation to youth cultural identity in late 1970s and early 1980s Britain. By examining the six compilation albums released to promote Oi! as a distinct strand of punk, it seeks to challenge prevailing dismissals of the genre as inherently racist or bound to the politics of the far right. Rather, Oi! – like punk more generally – was a contested cultural form. It was, moreover, centred primarily on questions of class and locality. To this end, Oi! sought to realize the working-class rebellion of punk’s early aesthetic; to give substance to its street-level pretentions and offer a genuine ‘song from the streets’.

O6-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat

Scope Epidemiological and clinical studies have demonstrated that the consumption of red haem-rich meat may contribute to the risk of colorectal cancer. Two hypotheses have been put forward to explain this causal relationship, i.e. N-nitroso compound (NOC) formation and lipid peroxidation (LPO). Methods and Results In this study, the NOC-derived DNA adduct O6-carboxymethylguanine (O6-CMG) and the LPO product malondialdehyde (MDA) were measured in individual in vitro gastrointestinal digestions of meat types varying in haem content (beef, pork, chicken). While MDA formation peaked during the in vitro small intestinal digestion, alkylation and concomitant DNA adduct formation was observed in seven (out of 15) individual colonic digestions using separate faecal inocula. From those, two haem-rich meat digestions demonstrated a significantly higher O6-CMG formation (p < 0.05). MDA concentrations proved to be positively correlated (p < 0.0004) with haem content of digested meat. The addition of myoglobin, a haem-containing protein, to the digestive simulation showed a dose–response association with O6-CMG (p = 0.004) and MDA (p = 0.008) formation. Conclusion The results suggest the haem-iron involvement for both the LPO and NOC pathway during meat digestion. Moreover, results unambiguously demonstrate that DNA adduct formation is very prone to inter-individual variation, suggesting a person-dependent susceptibility to colorectal cancer development following haem-rich meat consumption.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Polyphenols, glucosinolates, dietary fibre and colon cancer: Understanding the potential of specific types of fruit and vegetables to reduce bowel cancer progression

Colorectal cancer is the third most prevalent cancer worldwide and the most common diet-related cancer, influenced by diets rich in red meat, low in plant foods and high in saturated fats. Observational studies have shown that fruit and vegetable intake may reduce colorectal cancer risks, although the precise bioactive components remain unclear. This review will outline the evidence for the role of polyphenols, glucosinolates and fibres against cancer progression in the gastrointestinal tract. Those bioactive compounds are considered protective agents against colon cancer, with evidence taken from epidemiological, human clinical, animal and in vitro studies. Various mechanisms of action have been postulated, such as the potential of polyphenols and glucosinolates to inhibit cancer cell growth and the actions of insoluble fibres as prebiotics and the evidence for these actions are detailed within. In addition, recent evidence suggests that polyphenols also have the potential to shift the gut ecology in a beneficial manner. Such actions of both fibre and polyphenols in the gastrointestinal tract and through interaction with gut epithelial cells may act in an additive manner to help explain why certain fruits and vegetables, but not all, act to differing extents to inhibit cancer incidence and progression. Indeed, a focus on the individual actions of such fruit and vegetable components, in particular polyphenols, glucosinolates and fibres is necessary to help explain which components are active in reducing gastrointestinal cancer risk.

Poor survival on an artificial diet of two genotypes of the aphid Myzus persicae: a fitness cost of insecticide resistance?

A fully susceptible genotype (4106A) of Myzus persicae survived the longest on an artificial diet and, in several of the eight replicates, monitoring was terminated when the culture was still thriving. A genotype with elevated carboxylesterase FE4 at the R3 level (800F) had a mean survival of only 98.13 days, whereas 794J, which combines R3 E4 carboxylesterase with target-site resistance (knockdown resistance), survived for the even shorter mean time of 84.38 days. The poorer survival of the two genotypes with extremely elevated carboxylesterase-resistance was not the result of a reluctance to transfer to new diet at each diet change. Although available for only two replicates, a revertant clone of 794J (794Jrev), which has the same genotype as 794J but the amplified E4 genes are not expressed leading to a fully susceptible phenotype, did not appear to survive any better than this clone. This suggests that the poor survival on an artificial diet of the extreme-carboxylesterase genotypes is not the result of the cost of over-producing the enzyme. The frequency of insecticide-resistant genotypes is low in the population until insecticide is applied, indicating that they have reduced fitness, although this does not necessarily reflect a direct cost of expressing the resistance mechanism.

A pilot study investigating the effects of a single dose of a flavonoid-rich blueberry drink on memory in 8-10 year old children

Recent evidence from animal and adult human subjects has demonstrated potential benefits to cognition from flavonoid supplementation. This study aimed to investigate whether these cognitive benefits extended to a sample of school-aged children. Using a cross-over design, with a wash out of at least seven days between drinks, fourteen 8-10 year old children consumed either a flavonoid-rich blueberry drink or matched vehicle. Two hours after consumption, subjects completed a battery of five cognitive tests comprising the Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and a Visual N-back. In comparison to vehicle, the blueberry drink produced significant improvements in the delayed recall of a previously learned list of words, showing for the first time a cognitive benefit for acute flavonoid intervention in children. However, performance on a measure of proactive interference indicated that the blueberry intervention led to a greater negative impact of previously memorised words on the encoding of a set of new words. There was no benefit of our blueberry intervention for measures of attention, response inhibition or visuo-spatial memory. While findings are mixed, the improvements in delayed recall found in this pilot study suggest that, following acute flavonoid-rich blueberry interventions, school aged children encode memory items more effectively.

The effect of artificial diet on the production of alarm pheromone by Myzus persicae.

The cornicle secretion of Myzus persicae reared on artificial diet only elicits an alarm response in plant-reared conspecifics after the young aphids have been transferred to plants for 7days. Acetate in the form of 0.32% sodium acetate has been added to the diet as an early step in synthesis of the alarm pheromone, (E)-β-farnesene (EBF). The cornicle secretion of diet-reared aphids then elicits an alarm response. However, there is no difference in internal EBF concentration between plant- and diet-reared aphids. Puncturing aphids, either plant- or diet-reared, with a pin shows that both can elicit an alarm response, whereas it is reduced by half with diet-reared individuals. Although there is no significant difference in the concentration of EBF produced, the total amount in diet-reared aphids is increased by acetate in the diet to a level similar to that in plant-reared individuals: the size of aphids reared on an acetate-supplemented diet is increased and comparable with the size of those that are plant-reared. Bioassays with a range of EBF concentrations show a high threshold for the alarm response. It is concluded that the different size of aphids reared on plants and standard diet results in them secreting, respectively, above and below the response threshold.

A central role for heme iron in colon carcinogenesis associated with red meat intake

Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP+MeIQx, 50+25 μg/kg in diet) and NOC (induced by NaNO2+NaNO3 0.17+0.23 g/l of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically-induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc- deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67±39 mm2; 2,5% hemoglobin diet: 114±47 mm2, p=0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation.

EISCAT/CRRES observations: nightside ionospheric ion outflow and oxygen-rich substorm injections

We present combined observations made near midnight by the EISCAT radar, all-sky cameras and the combined released and radiation efects satellite (CRRES) shortly before and during a substorm. In particular, we study a discrete, equatorward-drifting auroral arc, seen several degrees poleward of the onset region. The arc passes through the field-aligned beam of the EISCAT radar and is seen to be associated with a considerable upflow of ionospheric plasma. During the substorm, the CRRES satellite observed two major injections, 17 min apart, the second of which was dominated by O+ ions. We show that the observed are was in a suitable location in both latitude and MLT to have fed O+ ions into the second injection and that the upward flux of ions associated with it was sufficient to explain the observed injection. We interpret these data as showing that arcs in the nightside plasma-sheet boundary layer could be the source of O+ ions energised by a dipolarisation of the mid- and near-Earth tail, as opposed to ions ejected from the dayside ionosphere in the cleft ion fountain.

Diet and lifestyle in Bronze Age Northwest Spain: the collective burial of Cova do Santo

A multidisciplinary investigation of the collective burial of Cova do Santo is presented as a novel approach to understand daily life during the Bronze Age in Northwest Iberia. The research is focused on three main aspects: i) taphonomy and patterns of disposal, ii) paleopathology and -demography as indicators of health status and lifestyle, and iii) stable isotope analysis to reconstruct paleodiet and to investigate the timing of the introduction of millet to the Iberian Peninsula. Osteological analyses were performed on 64 bones (61 human and 3 animal); additionally, bone collagen was extracted from 15 samples (13 human and 2 animal) and analyzed for its carbon and nitrogen stable isotopes composition. The radiocarbon age of the human remains is consistent with the Middle Bronze Age (c. 1890 to 1600 cal BC). The recovered remains belonged to a minimum number of 14 individuals with an estimated age at death of forty years or younger. This relatively young age is in contrast to a high prevalence of degenerative joint disease in the group. The isotopic results suggest a very homogeneous diet, which was almost exclusively based on C3 plants and terrestrial animal products. Overall, the data suggest that the studied population belonged to a period prior to the introduction of spring or summer-grown crops such as millets. The collective burial from the cave of Cova de Santo, Galicia, currently represents the largest assemblage of prehistoric human remains from Northwest Spain and the relatively good preservation of the bones offers a unique opportunity to investigate daily life in Northern Iberia during the Bronze Age.

Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk randomised, double-blind, placebo-controlled trial in healthy older adults

Background: Research indicates that chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although, there has been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. Objective: To investigate whether eight weeks of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. Design: High flavanone (HF: 305mg) 100% orange juice and equicaloric low flavanone (LF: 37mg) orange flavored cordial (500ml) were consumed daily for eight weeks by thirty seven healthy older adults (mean age 67 years) according to a crossover, double blind, randomized design separated by a four week washout. Cognitive function, mood and blood pressure were assessed at baseline and follow up with standardized validated tests. Results: Global cognitive function was significantly better following eight week consumption of flavanone-rich juice relative to eight week consumption of the low flavanone control. No significant effects on mood or blood pressure were observed. Conclusions: Chronic daily consumption of flavanone-rich 100% orange juice over eight weeks is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in ageing and the mechanisms which underlie these effects should be investigated.

Perylene as an electron-rich moiety in healable, complementary π–π stacked, supramolecular polymer systems

A two-component, supramolecular polymer blend has been designed using a novel π-electron rich bisperylene- terminated polyether. This polymer is able to self-assemble through electronically complementary π–π stacking interactions with a π-electron-deficient chain-folding polydiimide to afford thermally healable polymer blends. Model compounds were developed to assess the suitability of the deep green complexes formed between perylene residues and chain-folding bis-diimides for use in polymer blends. The polymer blends thus synthesised were elastomeric in nature and demonstrated healable properties as demonstrated by scanning electron microscopy. Healing was observed to occur rapidly at ca. 75 degC, and excellent healing efficiencies were found by tensometric and rheometric analyses. These tuneable, stimuli-responsive, supramolecular polymer blends are compared to related healable blends featuring pyrene-terminated oligomers.

The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial

Rationale: There has recently been increasing interest in the potential of flavanols, plant derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus stimulating neuronal function. Objectives: The present study employed arterial spin labelling (ASL) functional magnetic resonance imaging (FMRI) to explore the effect of a single acute dose of cocoa flavanols on regional CBF. Methods: CBF was measured pre and post consumption of low (23mg) or high (494mg) 330ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomised counterbalanced crossover double-blind design in eight males and ten females, aged 50-65 years. Changes in perfusion from pre to post consumption were calculated as a function of each drink. Results: Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex (ACC) and the central opercular cortex of the parietal lobe. Conclusions: Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance.

Apples and cardiovascular health: is the gut microbiota a core consideration?

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease. Human and animal intervention studies demonstrate beneficial effects on lipid metabolism, vascular function and inflammation but only a few studies have attempted to link these mechanistically with the gut microbiota. This review will focus on the reciprocal interaction between apple components and the gut microbiota, the potential link to cardiovascular health and the possible mechanisms of action.