The Effects of Dietary Polyphenols on Circulating Cardiovascular Disease Biomarkers and Iron Status:A Systematic Review

The prevalence of cardiovascular disease (CVD) is rising worldwide, remaining the major cause of death in developed countries. Polyphenols have been shown to have cardioprotective properties; however, their impact on iron bioavailability and potential impact on other aspects of health is unclear. A systematic review was undertaken to evaluate the current status of the relationship between habitual polyphenol consumption, iron status, and circulating biomarkers of CVD. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines, searches were performed across 5 electronic databases (PubMed, Cochrane Library, Scopus, Web of Science, and CINAHL) to identify randomized controlled trials which investigated the effects of polyphenol consumption on inflammatory markers, serum lipid profile, and iron absorption and bioavailability. In total, 1174 records were identified, with only 7 studies meeting the inclusion criteria. The selected studies involved 133 participants and used a variety of foods and supplements, including olive oil and cherries, rich in polyphenols including hydroxytyrosol, quercetin, and resveratrol, as well as catechin enriched drinks. The duration of the studies ranged from between 56 and 145 days, with total polyphenolic content of the food items and supplements ranging from 45 to 1015 mg (per 100 g). Polyphenols did not appear to interfere with iron status, and most studies reported improvements in inflammatory markers and lipid profile. While these results are promising, the limited number of studies and considerable heterogeneity across the interventions support the need for more extensive trials assessing the relationship between polyphenol intake, iron bioavailability, and CVD risk

Siderophore Biosynthesis But Not Reductive Iron Assimilation Is Essential for Aspergillus fumigatus Virulence

The ability to acquire iron in vivo is essential for most microbial pathogens. Here we show that Aspergillus fumigatus does not have specific mechanisms for the utilization of host iron sources. However, it does have functional siderophore-assisted iron mobilization and reductive iron assimilation systems, both of which are induced upon iron deprivation. Abrogation of reductive iron assimilation, by inactivation of the high affinity iron permease (FtrA), has no effect on virulence in a murine model of invasive aspergillosis. In striking contrast, A. fumigatus l-ornithine-N 5-monooxygenase (SidA), which catalyses the first committed step of hydroxamate-type siderophore biosynthesis, is absolutely essential for virulence. Thus, A. fumigatus SidA is an essential virulence attribute. Combined with the absence of a sidA ortholog—and the fungal siderophore system in general—in mammals, these data demonstrate that the siderophore biosynthetic pathway represents a promising new target for the development of antifungal therapies

The Translation of Japanese Literature in Spain

10 páginas, 3 figuras, I figura, 1 tabla -- PAGS nros. 291-300Many fungi grow over a wide pH range and their gene expression is tailored to the environmental pH. In Aspergillus nidulans, the transcription factor PacC, an activator of genes expressed in alkaline conditions and a repressor of those expressed in acidic conditions, undergoes two processing proteolyses, the first being pH-signal dependent and the second proteasomal. Signal transduction involves a 'go-between' connecting two complexes, one of which comprises two plasma membrane proteins and an arrestin and the other comprises PacC, a cysteine protease, a scaffold and endosomal components. The Saccharomyces cerevisiae PacC orthologue, Rim101p, differs in that it does not undergo the second round of proteolysis and it functions directly as a repressor only. PacC/Rim101-mediated pH regulation is crucial to fungal pathogenicityPeer reviewe

A gene to organism approach--assessing the impact of environmental pollution in eelpout (Zoarces viviparus) females and larvae

A broad biomarker approach was applied to study the effects of marine pollution along the Swedish west coast using the teleost eelpout (Zoarces viviparus) as the sentinel species. Measurements were performed on different biological levels, from the molecular to the organismal, including measurements of messenger RNA (mRNA), proteins, cellular and tissue changes, and reproductive success. Results revealed that eelpout captured in Stenungsund had significantly higher hepatic ethoxyresorufin O-deethylase activity, high levels of both cytochrome P4501A and diablo homolog mRNA, and high prevalence of dead larvae and nuclear damage in erythrocytes. Eelpout collected in Göteborg harbor displayed extensive macrovesicular steatosis, whereby the majority of hepatocytes were affected throughout the liver, which could indicate an effect on lipid metabolism. Results also indicate that eelpouts collected at polluted sites might have an affected immune system, with lower mRNA expression of genes involved in the innate immune system and a higher number of lymphocytes. Biomarker assessment also was performed on livers dissected from unborn eelpout larvae collected from the ovary of the females. No significant differences were noted, which might indicate that the larvae to some extent are protected from effects of environmental pollutants. In conclusion, usage of the selected set of biological markers, covering responses from gene to organism, has demonstrated site-specific biomarker patterns that provided a broad and comprehensive picture of the impact of environmental stressors

How to humiliate and shame: A reporter's guide to the power of the mugshot

This is an Author's Accepted Manuscript of an article published in Social Semiotics, 24(1), 56-87, 2014, copyright Taylor & Francis, available online at: http://www.tandfonline.com/The judicial photograph – the “mugshot” – is a ubiquitous and instantly recognisable form, appearing in the news media, on the internet, on book covers, law enforcement noticeboards and in many other mediums. This essay attempts to situate the mugshot in a historical and theoretical context to explain the explicit and implicit meaning of the genre as it has developed, focussing in particular on their use in the UK media in late modernity. The analysis is based on the author's reflexive practice as a journalist covering crime in the national news media for 30 years and who has used mugshots to illustrate stories for their explicit and specific content. The author argues that the visual limitations of the standardised “head and shoulders” format of the mugshot make it a robust subject for analysing the changing meaning of images over time. With little variation in the image format, arguments for certain accreted layers of signification are easier to make. Within a few years of the first appearance of the mugshot form in the mid-19th century, it was adopted and adapted as a research tool by scientists and criminologists. While the positivist scientists claimed empirical objectivity we can now see that mugshots played a part in the construction of subjective notions of “the other”, “the lesser” or “sub-human” on the grounds of class, race and religion. These dehumanising ideas later informed the theorists and bureaucrats of National Socialist ideology from the 1920s to 1940s. The author concludes that once again the mugshot has become, in certain parts of the media, a signifier widely used to exclude or deride certain groups. In late modernity, the part of the media that most use mugshots – the tabloid press and increasingly tabloid TV – is part of a neo-liberal process that, in a conscious commercial appeal to the paying audience, seeks to separate rather than unify wider society

A qualitative study of stakeholders' perspectives on the social network service environment

Over two billion people are using the Internet at present, assisted by the mediating activities of software agents which deal with the diversity and complexity of information. There are, however, ethical issues due to the monitoring-and-surveillance, data mining and autonomous nature of software agents. Considering the context, this study aims to comprehend stakeholders' perspectives on the social network service environment in order to identify the main considerations for the design of software agents in social network services in the near future. Twenty-one stakeholders, belonging to three key stakeholder groups, were recruited using a purposive sampling strategy for unstandardised semi-structured e-mail interviews. The interview data were analysed using a qualitative content analysis method. It was possible to identify three main considerations for the design of software agents in social network services, which were classified into the following categories: comprehensive understanding of users' perception of privacy, user type recognition algorithms for software agent development and existing software agents enhancement

A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma.

Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines. We identified 548 likely oncogenic mutations in 182 genes. By integrating published data sets of NGS in MM, we retrieved a list of genes with significant relevance to myeloma and found that the mutational spectrum of primary samples and MM cell lines is partially overlapping. Gains and losses of chromosomes, chromosomal segments and gene loci were identified with accuracy comparable to conventional arrays, allowing identification of lesions with known prognostic significance. Furthermore, we identified IGH translocations with high positive and negative predictive value. Our approach could allow the identification of novel biomarkers with clinical relevance in myeloma

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia

Context: Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albuminwith increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals. Objective: Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. Design and Results: Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. 125I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T 4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated. Conclusions: A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein