Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses

Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is a severe metabolic disorder caused by accumulation of heparan sulfate (HS), one of glycosaminoglycans (GAGs), due to a genetic defect resulting in a deficiency of GAG hydrolysis. This disorder is characterized as the most severe neurological form of MPS, revealing rapid deterioration of brain functions. Among therapeutic approaches for MPS III, one of the most promising appears to be the substrate reduction therapy (SRT). Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is an isoflavone that has been used in SRT for MPS III. In this report, we tested effects of other flavonoids (apigenin, daidzein, kaempferol and naringenin) on GAG synthesis. Their cytotoxicity and anti-proliferation features were also tested. We found that daidzein and kaempferol inhibited GAG synthesis significantly. Moreover, these compounds were able to reduce lysosomal storage in MPS IIIA fibroblasts. Interestingly, although genistein is believed to inhibit GAG synthesis by blocking the tyrosine kinase activity of the epidermal growth factor receptor, we found that effects of other flavonoids were not due to this mechanism. In fact, combinations of various flavonoids resulted in significantly more effective inhibition of GAG synthesis than the use of any of these compounds alone. These results, together with results published recently by others, suggest that combination of flavonoids can be considered as a method for improvement of efficiency of SRT for MPS III

Ragweed as an Example of Worldwide Allergen Expansion

<p/> <p>Multiple factors are contributing to the expansion of ragweed on a worldwide scale. This review seeks to examine factors that may contribute to allergen expansion with reference to ragweed as a well-studied example. It is our hope that increased surveillance for new pollens in areas not previously affected and awareness of the influence the changing environment plays in allergic disease will lead to better outcomes in susceptible patients.</p

Threat of allergenic airborne grass pollen in Szczecin, NW Poland: the dynamics of pollen seasons, effect of meteorological variables and air pollution

The dynamics of Poaceae pollen season, in particularly that of the Secale genus, in Szczecin (western Poland) 2004–2008 was analysed to establish a relationship between the meteorological variables, air pollution and the pollen count of the taxa studied. Consecutive phases during the pollen season were defined for each taxon (1, 2.5, 5, 25, 50, 75, 95, 97.5, 99% of annual total), and duration of the season was determined using the 98% method. On the basis of this analysis, the temporary differences in the dynamics of the seasons were most evident for Secale in 2005 and 2006 with the longest main pollen season (90% total pollen). The pollen season of Poaceae started the earliest in 2007, when thermal conditions were the most favourable. Correlation analysis with meteorological factors demonstrated that the relative humidity, mean and maximum air temperature, and rainfall were the factors influencing the average daily pollen concentrations in the atmosphere; also, the presence of air pollutants such as ozone, PM10 and SO2 was statistically related to the pollen count in the air. However, multiple regression models explained little part of the total variance. Atmospheric pollution induces aggravation of symptoms of grass pollen allergy

Identifying evidence for past mining and metallurgy from a record of metal contamination preserved in an ombrotrophic mire near Leadhills, SW Scotland, UK

This study presents a new 3600-year record of past metal contamination from a bog located close to the Leadhills and Wanlockhead orefield of southwest Scotland. A peat core, collected from Toddle Moss, was radiocarbon (14C) dated and analysed for trace metal concentrations (by EMMA) and lead isotopes (by ICP-MS) to reconstruct the atmospheric deposition history of trace metal contamination, in particular, lead. The results show good agreement with documented historical and archaeological records of mining and metallurgy in the region: the peak in metal mining during the 18th century, the decline of lead mining during the Anglo-Scottish war and lead smelting during the early medieval period. There may also have been earlier workings during the Late Bronze and Iron Ages indicated by slight increases in lead concentrations, the Pb/Ti ratio and a shift in 206Pb/207Pb ratios, which compare favourably to the signatures of a galena ore from Leadhills and Wanlockhead. In contrast to other records across Europe, no sizeable lead enrichment was recorded during the Roman Iron Age, suggesting that the orefield was not a significant part of the Roman lead extraction industry in Britain. These findings add to the various strands of archaeological evidence that hint at an early lead extraction and metallurgical industry based in southern Scotland. The results also provide further evidence for specific regional variations in the evolution of mining and metallurgy and an associated contamination signal during prehistoric and Roman times across Europe

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph

Evaluating Practitioner Training to Improve Competencies and Organizational Practices for Engaging Fathers in Parenting Interventions.

Fathers are consistently underrepresented in parenting interventions and practitioners are an important target for change in interventions to enhance father engagement. This research examined the effects of two practitioner training programs in improving practitioner rated competencies and organizational father-inclusive practices. Two studies were conducted, each with a single group, repeated measures (pre, post and 2-month follow-up) design. Study 1 (N = 233) examined the outcomes of face-to-face training in improving practitioner ratings of competencies in engaging fathers, perceived effectiveness and use of father engagement strategies, organizational practices and rates of father engagement. Study 2 (N = 356) examined online training using the same outcome measures. Practitioners in both training formats improved in their competencies, organizational practices and rates of father engagement over time, yet those in the online format deteriorated in three competencies from post-training to follow-up. The implications for delivering practitioner training programs to enhance competencies and rates of father engagement are discussed