The emergence of international food safety standards and guidelines: understanding the current landscape through a historical approach

Following the Second World War, the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) teamed up to construct an International Codex Alimentarius (or 'food code') which emerged in 1963. The Codex Committee on Food Hygiene (CCFH) was charged with the task of developing microbial hygiene standards, although it found itself embroiled in debate with the WHO over the nature these standards should take. The WHO was increasingly relying upon the input of biometricians and especially the International Commission on Microbial Specifications for Foods (ICMSF) which had developed statistical sampling plans for determining the microbial counts in the final end products. The CCFH, however, was initially more focused on a qualitative approach which looked at the entire food production system and developed codes of practice as well as more descriptive end-product specifications which the WHO argued were 'not scientifically correct'. Drawing upon historical archival material (correspondence and reports) from the WHO and FAO, this article examines this debate over microbial hygiene standards and suggests that there are many lessons from history which could shed light upon current debates and efforts in international food safety management systems and approaches

Avian Influenza Viruses Infect Primary Human Bronchial Epithelial Cells Unconstrained by Sialic Acid α2,3 Residues

Avian influenza viruses (AIV) are an important emerging threat to public health. It is thought that sialic acid (sia) receptors are barriers in cross-species transmission where the binding preferences of AIV and human influenza viruses are sias α2,3 versus α2,6, respectively. In this study, we show that a normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N1, H5N2 and H5N3 AIV, which primarily bind to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface. NHBE cells treated with neuraminidase prior to infection are infected by AIV despite removal of sia α2,3 moieties. Following AIV infection, higher levels of IP-10 and RANTES are secreted compared to human influenza virus infection, indicating differential chemokine expression patterns, a feature that may contribute to differences in disease pathogenesis between avian and human influenza virus infections in humans

Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations

Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones

Genomic Analysis of QTLs and Genes Altering Natural Variation in Stochastic Noise

Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic loci are distributed within the genome. Understanding these questions is critical to our understanding of quantitative traits and how they relate to the underlying causal loci, especially since stochastic noise may be directly influenced by underlying changes in the wiring of regulatory networks. We identified QTLs controlling natural variation in stochastic noise of glucosinolates, plant defense metabolites, as well as QTLs for stochastic noise of related transcripts. These loci included stochastic noise QTLs unique for either transcript or metabolite variation. Validation of these loci showed that genetic polymorphism within the regulatory network alters stochastic noise independent of effects on corresponding average levels. We examined this phenomenon more globally, using transcriptomic datasets, and found that the Arabidopsis transcriptome exhibits significant, heritable differences in stochastic noise. Further analysis allowed us to identify QTLs that control genomic stochastic noise. Some genomic QTL were in common with those altering average transcript abundance, while others were unique to stochastic noise. Using a single isogenic population, we confirmed that natural variation at ELF3 alters stochastic noise in the circadian clock and metabolism. Since polymorphisms controlling stochastic noise in genomic phenotypes exist within wild germplasm for naturally selected phenotypes, this suggests that analysis of Arabidopsis evolution should account for genetic control of stochastic variance and average phenotypes. It remains to be determined if natural genetic variation controlling stochasticity is equally distributed across the genomes of other multi-cellular eukaryotes

A systematic review of fantasy driven vs. contact driven internet-initiated sexual offences: Discrete or overlapping typologies?

Data presented within this article supports the findings of the manuscript “A systematic review of fantasy driven vs contact driven internet-initiated sexual offences: Discrete or overlapping typologies?” (Broome et al., in press) [1]. Inclusion and Exclusion criteria of study selection, PICO Formulation of Study Appraisal, as well as the Study Characteristics and Methodology of included studies are presented

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Effects of psychological and psychosocial interventions on sport performance:a meta-analysis

Background: Psychologists are increasingly supporting the quest for performance enhancement in sport and there is a need to evaluate the evidence base underpinning their work. Objectives: To synthesize the most rigorous available research that has evaluated psychological, social, and psychosocial interventions with sport performers on variables relating to their athletic performance, and to address some of the perplexing issues in the sport psychology intervention literature (e.g., do interventions have a lasting effect on sport performance?). Methods: Randomized controlled trials were identified through electronic databases, hand-searching volumes of pertinent journals, scrutinizing reference lists of previous reviews, and contacting experts in the evaluation of interventions in this field. Included studies were required to evaluate the effects of psychological, social, or psychosocial interventions on sport performance in athletes when compared to a no-treatment or placebo-controlled treatment comparison group. A random effects meta-analysis calculating the standardized mean difference (Hedges’ g), meta-regressions, and trim and fill analyses were conducted. Data were analyzed at post-test and follow-up (ranging from 1 to 4 weeks after the intervention finished) assessments. Results: Psychological and psychosocial interventions were shown to enhance sport performance at post-test (k = 35, n = 997, Hedges’ g = 0.57, 95 % CI = 0.22–0.92) and follow-up assessments (k = 8, n = 189, Hedges’ g = 1.16, 95 % CI = 0.25–2.08); no social interventions were included or evaluated. Larger effects were found for psychosocial interventions and there was some evidence that effects were greatest in coach-delivered interventions and in samples with a greater proportion of male participants. Conclusions: Psychological and psychosocial interventions have a moderate positive effect on sport performance, and this effect may last at least a month following the end of the intervention. Future research would benefit from following guidelines for intervention reporting