Antioxidant and free radical scavenging activity of isoflavone metabolites

1. Soy isoflavones have been extensively studied because of their possible health-promoting effects. Genistein and daidzein, the major isoflavone aglycones, have received most attention; however, they undergo extensive metabolism in the gut and liver, which might affect their biological properties. 2. The antioxidant activity, free radical-scavenging properties and selected cellular effects of the isoflavone metabolites equol, 8-hydroxydaidzein, O-desmethylangiolensin, and 1,3,5 trihydroxybenzene were investigated in comparison with their parent aglycones, genistein and daidzein. 3. Electron spin resonance spectroscopy indicated that 8-hydroxydaidzein was the most potent scavenger of hydroxyl and superoxide anion radicals. Isoflavone metabolites also exhibited higher antioxidant activity than parent compounds in standard antioxidant (FRAP and TEAC) assays. However, for the suppression of nitric oxide production by activated macrophages, genistein showed the highest potency, followed by equol and daidzein. 4. The metabolism of isoflavones affects their free radical scavenging and antioxidant properties, and their cellular activity, but the effects are complex.

Reclassification of Bacteroides putredinis (Weinberg et al., 1937) in a New Genus Alistipes gen. nov., as Alistipes putredinis comb. nov., and description of Alistipes finegoldii sp nov., from human sources

During studies on the bacteriology of appendicitis in children, we often isolated from inflamed and non-inflamed tissue samples, an unusual bile-resistant pigment-producing strictly anaerobic gram-negative rod. Phenotypically this organism resembles members of Bacteroides fragilis group of species, as it is resistant to bile and exhibits a special-potency-disk pattern (resistance to vancomycin, kanamycin and colistin) typical for the B. fragilis group. However, the production of brown pigment on media containing haemolysed blood and a cellular fatty acid composition dominated by iso-C15:0, suggests that the organism most closely resembles species of the genus Porphyromonas. However, the unidentified organism differs from porphyromonads by being bile-resistant and by not producing butyrate as a metabolic end-product. Comparative 16S ribosomal RNA gene sequencing studies show the unidentified organism represents a distinct sub-line, associated with but distinct from, the miss-classified species Bacteroides putredinis. The clustering of the unidentified bacterium with Bacteroides putredinis was statistically significant, but they displayed >4% sequence divergence with each other. Chromosomal DNA-DNA pairing studies further confirmed the separateness of the unidentified bacterium and Bacteroides putredinis. Based on phenotypic and phylogenetic considerations, it is proposed that Bacteroides putredinis and the unidentified bacterium from human sources be classified in a new genus Alistipes, as Alistipes putredinis comb. nov. and Alistipes finegoldii sp. nov., respectively. The type strain of Alistipes finegoldii is CCUG 46020(T) (= AHN2437(T)).

Green tea (Camellia sinensis) catechins and vascular function

The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life.

Bifidobacteria in the infant faecal microbiota have been the focus of much interest, especially during the exclusive milk-feeding period and in relation to the fortification of infant formulae to better mimic breast milk. However, longitudinal studies examining the diversity and dynamics of the Bifidobacterium population of infants are lacking, particularly in relation to the effects of weaning. Using a polyphasic strategy, the Bifidobacterium populations of breast- and formula-fed infants were examined during the first 18 months of life. Bifidobacterium-specific denaturing gradient gel electrophoresis demonstrated that breast-fed infants harboured greater diversity than formula-fed infants and the diversity of the infants' Bifidobacterium populations increased with weaning. Twenty-seven distinctive banding profiles were observed from ∼1100 infant isolates using ribosomal intergenic spacer analysis, 14 biotypes of which were confirmed to be members of the genus Bifidobacterium. Two profiles (H, Bifidobacterium longum subsp. infantis; and I, Bifidobacterium bifidum) were common culturable biotypes, seen in 9/10 infants, while profile E (Bifidobacterium breve) was common among breast-fed infants. Overall, inter- and intra-individual differences were observed in the Bifidobacterium populations of infants between 1 and 18 months of age, although weaning was associated with increased diversity of the infant Bifidobacterium populations. Breast-fed infants generally harboured a more complex Bifidobacterium microbiota than formula-fed infants.

Longitudinal investigation of the faecal microbiota of healthy full-term infants using fluorescence in situ hybridization and denaturing gradient gel electrophoresis.

From birth onwards, the gastrointestinal (GI) tract of infants progressively acquires a complex range of micro-organisms. It is thought that by 2 years of age the GI microbial population has stabilized. Within the developmental period of the infant GI microbiota, weaning is considered to be most critical, as the infant switches from a milk-based diet (breast and/or formula) to a variety of food components. Longitudinal analysis of the biological succession of the infant GI/faecal microbiota is lacking. In this study, faecal samples were obtained regularly from 14 infants from 1 month to 18 months of age. Seven of the infants (including a set of twins) were exclusively breast-fed and seven were exclusively formula-fed prior to weaning, with 175 and 154 faecal samples, respectively, obtained from each group. Diversity and dynamics of the infant faecal microbiota were analysed by using fluorescence in situ hybridization and denaturing gradient gel electrophoresis. Overall, the data demonstrated large inter- and intra-individual differences in the faecal microbiological profiles during the study period. However, the infant faecal microbiota merged with time towards a climax community within and between feeding groups. Data from the twins showed the highest degree of similarity both quantitatively and qualitatively. Inter-individual variation was evident within the infant faecal microbiota and its development, even within exclusively formula-fed infants receiving the same diet. These data can be of help to future clinical trials (e.g. targeted weaning products) to organize protocols and obtain a more accurate outline of the changes and dynamics of the infant GI microbiota.

Therapeutic and cytotoxic effects of the novel antipsoriasis codrug, naproxyl-dithranol, on HaCaT cells

A novel topical codrug, naproxyl–dithranol (Nap-DTH), in which dithranol and naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity, was synthesized. The antiproliferative, anti-inflammatory and toxic effects of Nap-DTH were assessed, at the cellular level, using various in vitro methods. Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects were compared with those of the parent compounds, individually and as a 1:1 mixture of naproxen:dithranol to mimic 1:1 in situ liberation from Nap-DTH. The results demonstrate that Nap-DTH did not modify proliferation and only exhibited slight toxic effects after 24 h at concentrations >21 μM. At a lower concentration (3.4 μM), Nap-DTH did not alter cell proliferation or inflammation, which suggests that the codrug is therapeutically inert. Relating to this, the 1:1 mixture of naproxen:dithranol exhibited the lowest toxic effect and the highest antiproliferative effect on HaCaT keratinocytes compared to dithranol at the same concentration. Moreover, the 1:1 mixture exhibited a reduced inflammatory effect compared to dithranol alone, as reflected by the upregulation of cyclooxygenase-2 by 45% and 136%, respectively. In spite of the 1:1 mixture showing a greater downregulation of Ki-67 and a 2-fold reduction of proliferating cell nuclear antigen (both cellular markers of proliferation) than dithranol, dithranol showed a much greater induction of cleaved caspase-3 protein expression (upregulated by 287%, compared to 85% for the 1:1 mixture). This suggests that when dithranol was administered with naproxen, inhibition of cell growth plays a more important role in the antiproliferation effects than the induction of apoptotic cell death. These results confirm that the codrug would lead to a better therapeutic profile and fewer adverse effects compared to its parent compounds.

Winckelmann and the invention of antiquity: history and aesthetics in the age of Altertumswissenschaft

This volume provides a new perspective on the emergence of the modern study of antiquity, Altertumswissenschaft, in eighteenth-century Germany through an exploration of debates that arose over the work of the art historian Johann Joachim Winckelmann between his death in 1768 and the end of the century. This period has long been recognised as particularly formative for the development of modern classical studies, and over the past few decades has received increased attention from historians of scholarship and of ideas. Winckelmann's eloquent articulation of the cultural and aesthetic value of studying the ancient Greeks, his adumbration of a new method for studying ancient artworks, and his provision of a model of cultural-historical development in terms of a succession of period styles, influenced both the public and intra-disciplinary self-image of classics long into the twentieth century. Yet this area of Winckelmann's Nachleben has received relatively little attention compared with the proliferation of studies concerning his importance for late eighteenth-century German art and literature, for historians of sexuality, and his traditional status as a 'founder figure' within the academic disciplines of classical archaeology and the history of art. Harloe restores the figure of Winckelmann to classicists' understanding of the history of their own discipline and uses debates between important figures, such as Christian Gottlob Heyne, Friedrich August Wolf, and Johann Gottfried Herder, to cast fresh light upon the emergence of the modern paradigm of classics as Altertumswissenschaft: the multi-disciplinary, comprehensive, and historicizing study of the ancient world.

Competition and product survival in the UK car market

The paper examines the extent to which inter- and intra-firm competition influenced the survival of cars in the UK market between 1971 and 1998. It is shown that, while competition influenced product survival in all market segments within the UK car market, the nature of that competition differed between them. In the small family and large family car segments, intra-firm competition dominated inter-firm competition. In contrast, in the luxury/sports car segment only inter-firm competition conditions resulted in product survival. Evidence was also found that the luxury/sports car segment has grown more competitive over time and that firms marketing products in the family car segments have become considerably more successful at avoiding the effects of intra-firm competition.

Liability of country foreignness and liability of regional foreignness: their effects on geographic diversification and firm performance

The costs of inter- and intra-regional diversification have been widely discussed in the existing international business literature, but the findings are mixed. Explanations for the mixed findings have important managerial implications, because business managers have to estimate accurately the costs of doing business within and across regions before they make their internationalization decisions. To explain the existing mixed findings, this study differentiates between liabilities of foreignness at the country and regional levels, and explores the joint effects of liability of country foreignness (LCF) and liability of regional foreignness (LRF) on the performance of internationalizing firms. Using data from 167 Canadian firms, we find that LCF may not necessarily be negatively correlated with intra-regional diversification, but LRF is positively correlated with inter-regional diversification. LCF moderates the relationship between LRF and inter-regional diversification, and also mediates the relationship between intra-regional diversification and firm performance. LRF mediates the relationship between inter-regional diversification and firm performance. Missing one or more of these variables may result in different cost estimates. Identification of the relationships between these variables helps to improve the accuracy of estimating the costs of doing business aboard.

Struggles over family land? Tree crops, land and labour in Ghana's Brong-Ahafo region

Agricultural land use in much of Brong-Ahafo region, Ghana has been shifting from the production of food crops towards increased cashew nut cultivation in recent years. This article explores everyday, less visible, gendered and generational struggles over family farms in West Africa, based on qualitative, participatory research in a rural community that is becoming increasingly integrated into the global capitalist system. As a tree crop, cashew was regarded as an individual man's property to be passed on to his wife and children rather than to extended family members, which differed from the communal land tenure arrangements governing food crop cultivation. The tendency for land, cash crops and income to be controlled by men, despite women's and young people's significant labour contributions to family farms, and for women to rely on food crop production for their main source of income and for household food security, means that women and girls are more likely to lose out when cashew plantations are expanded to the detriment of land for food crops. Intergenerational tensions emerged when young people felt that their parents and elders were neglecting their views and concerns. The research provides important insights into gendered and generational power relations regarding land access, property rights and intra-household decision-making processes. Greater dialogue between genders and generations may help to tackle unequal power relations and lead to shared decision-making processes that build the resilience of rural communities.

Dystrophin analysis using a panel of anti-dystrophin antibodies in Duchenne and Becker muscular dystrophy.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in 19 patients with Xp21 disorders and in 25 individuals with non-Xp21 muscular dystrophy. Antibodies raised to seven different regions spanning most of the protein were used for immunocytochemistry. In all patients specific dystrophin staining anomalies were detected and correlated with clinical severity and also gene deletion. In patients with Becker muscular dystrophy (BMD) the anomalies detected ranged from inter- and intra-fibre variation in labelling intensity with the same antibody or several antibodies to general reduction in staining and discontinuous staining. In vitro evidence of abnormal dystrophin breakdown was observed reanalysing the muscle of patients, with BMD and not that of non-Xp21 dystrophies, after it has been stored for several months. A number of patients with DMD showed some staining but this did not represent a diagnostic problem. Based on the data presented, it was concluded that immunocytochemistry is a powerful technique in the prognostic diagnosis of Xp21 muscular dystrophies.

Explaining patterns of avian diversity and endemicity: climate and biomes of southern Africa over the last 140,000 years

Aim Test hypotheses that present biodiversity and endemic species richness are related to climatic stability and/or biome persistence.Location Africa south of 15° S. Methods Seventy eight HadCM3 general circulation model palaeoclimate experiments spanning the last 140,000 years, plus a pre-industrial experiment,were used to calculate measures of climatic variability for 0.5° grid cells. Models were fitted relating distributions of the nine biomes of South Africa,Lesotho and Swaziland to present climate. These models were used to simulate potential past biome distribution and extent for the 78 palaeoclimate experiments, and three measures of biome persistence. Climatic response surfaces were fitted for 690 bird species regularly breeding in the region and used to simulate present species richness for cells of the 0.5° grid. Species richness was evaluated for residents, mobile species (nomadic or partially/altitudinally migrant within the region), and intra-African migrants, and also separately for endemic/near-endemic (hereafter ‘endemic’) species as a whole and those associated with each biome. Our hypotheses were tested by analysing correlations between species richness and climatic variability or biome persistence. Results The magnitude of climatic variability showed clear spatial patterns. Marked changes in biome distributions and extents were projected, although limited areas of persistence were projected for some biomes. Overall species richness was not correlated with climatic variability, although richness of mobile species showed a weak negative correlation. Endemic species richness was significantly negatively correlated with climatic variability. Strongest correlations, however, were positive correlations between biome persistence and richness of endemics associated with individual biomes. Main conclusions Low climatic variability, and especially a degree of stability enabling biome persistence, is strongly correlated with species richness of birds endemic to southern Africa. This probably principally reflects reduced extinction risk for these species where the biome to which they are adapted persisted

Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Auriculo-condylar syndrome (ACS), an autosomal dominant disorder of first and second pharyngeal arches, is characterized by malformed ears (`question mark ears`), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia. Penetrance seems to be complete, but there is high inter-and intra-familial phenotypic variation, with no evidence of genetic heterogeneity. We herein describe a new multigeneration family with 11 affected individuals (F1), in whom we confirm intra-familial clinical variability. Facial asymmetry, a clinical feature not highlighted in other ACS reports, was highly prevalent among the patients reported here. The gene responsible for ACS is still unknown and its identification will certainly contribute to the understanding of human craniofacial development. No chromosomal rearrangements have been associated with ACS, thus mapping and positional cloning is the best approach to identify this disease gene. To map the ACS gene, we conducted linkage analysis in two large ACS families, F1 and F2 (F2; reported elsewhere). Through segregation analysis, we first excluded three known loci associated with disorders of first and second pharyngeal arches (Treacher Collins syndrome, oculo-auriculo-vertebral spectrum, and Townes-Brocks syndrome). Next, we performed a wide genome search and we observed evidence of linkage to 1p21.1-q23.3 in F2 (LOD max 3.01 at theta = 0). Interestingly, this locus was not linked to the phenotype segregating in F1. Therefore, our results led to the mapping of a first locus of ACS (ACS1) and also showed evidence for genetic heterogeneity, suggesting that there are at least two loci responsible for this phenotype.

Evolutionary history of Ramphastos toucans: Molecular phylogenetics, temporal diversification, and biogeography

The toucan genus Ramphastos (Piciformes: Ramphastidae) has been a model in the formulation of Neotropical paleobiogeographic hypotheses. Weckstein (2005) reported on the phylogenetic history of this genus based on three mitochondrial genes, but some relationships were weakly supported and one of the subspecies of R. vitellinus (citreolaemus) was unsampled. This study expands on Weckstein (2005) by adding more DNA sequence data (including a nuclear marker) and more samples, including R v. citreolaemus. Maximum parsimony, maximum likelihood, and Bayesian methods recovered similar trees, with nodes showing high support. A monophyletic R. vitellinus complex was strongly supported as the sister-group to R. brevis. The results also confirmed that the southeastern and northern populations of R. vitellinus ariel are paraphyletic. X v. citreolaemus is sister to the Amazonian subspecies of the vitellinus complex. Using three protein-coding genes (COI, cytochrome-b and ND2) and interval-calibrated nodes under a Bayesian relaxed-clock framework, we infer that ramphastid genera originated in the middle Miocene to early Pliocene, Ramphastos species originated between late Miocene and early Pleistocene, and intra-specific divergences took place throughout the Pleistocene. Parsimony-based reconstruction of ancestral areas indicated that evolution of the four trans-Andean Ramphastos taxa (R. v. citreolaemus, R. a. swainsonii, R. brevis and R. sulfuratus) was associated with four independent dispersals from the cis-Andean region. The last pulse of Andean uplift may have been important for the evolution of R. sulfuratus, whereas the origin of the other trans-Andean Ramphastos taxa is consistent with vicariance due to drying events in the lowland forests north of the Andes. Estimated rates of molecular evolution were higher than the ""standard"" bird rate of 2% substitutions/site/million years for two of the three genes analyzed (cytochrome-b and ND2). (C) 2009 Elsevier Inc. All rights reserved.