BZLF1, an Epstein–Barr virus immediate–early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function

AbstractWe have previously demonstrated that the Epstein–Barr virus immediate–early BZLF1 protein interacts with, and is inhibited by, the NF-κB family member p65. However, the effects of BZLF1 on NF-κB activity have not been intensively studied. Here we show that BZLF1 inhibits p65-dependent gene expression. BZLF1 inhibited the ability of IL-1, as well as transfected p65, to activate the expression of two different NF-κB-responsive genes, ICAM-1 and IκB-α. BZLF1 also reduced the constitutive level of IκB-α protein in HeLa and A549 cells, and increased the amount of nuclear NF-κB to a similar extent as tumor necrosis factor-alpha (TNF-α) treatment. In spite of this BZLF1-associated increase in the nuclear form of NF-κB, BZLF1 did not induce binding of NF-κB to NF-κB responsive promoters (as determined by chromatin immunoprecipitation assay) in vivo, although TNF-α treatment induced NF-κB binding as expected. Overexpression of p65 dramatically inhibited the lytic replication cycle of EBV in 293-EBV cells, confirming that NF-κB also inhibits BZLF1 transcriptional function. Our results are consistent with a model in which BZLF1 inhibits the transcriptional function of p65, resulting in decreased transcription of IκB-α, decreased expression of IκB-α protein, and subsequent translocation of NF-κB to the nucleus. This nuclear translocation of NF-κB may promote viral latency by negatively regulating BZLF1 transcriptional activity. In situations where p65 activity is limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65 transcriptional function may protect the virus from the host immune system during the lytic form of infection

When to start antiretroviral therapy in resource-limited settings: a human rights analysis

<p>Abstract</p> <p>Background</p> <p>Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration.</p> <p>Discussion</p> <p>According to our analysis, a policy of earlier ART initiation would better serve both public health and human rights objectives. We highlight a number of policy approaches that could be taken to help meet this aim, including increased international financial support, alternative models of care, and policies to secure the most affordable sources of appropriate antiretroviral drugs.</p> <p>Summary</p> <p>Widespread implementation of earlier ART initiation is challenging in resource-limited settings. Nevertheless, rationing of essential medicines is a restriction of human rights, and the principle of least restriction serves to focus attention on alternative measures such as adapting health service models to increase capacity, decreasing costs, and seeking additional international funding. Progressive realisation using well-defined steps will be necessary to allow for a phased implementation as part of a framework of short-term targets towards nationwide policy adoption, and will require international technical and financial support.</p

World input-output network

Production systems, traditionally analyzed as almost independent national systems, are increasingly connected on a global scale. Only recently becoming available, the World Input-Output Database (WIOD) is one of the first efforts to construct the global multi-regional input-output (GMRIO) tables. By viewing the world input-output system as an interdependent network where the nodes are the individual industries in different economies and the edges are the monetary goods flows between industries, we analyze respectively the global, regional, and local network properties of the so-called world input-output network (WION) and document its evolution over time. At global level, we find that the industries are highly but asymmetrically connected, which implies that micro shocks can lead to macro fluctuations. At regional level, we find that the world production is still operated nationally or at most regionally as the communities detected are either individual economies or geographically well defined regions. Finally, at local level, for each industry we compare the network-based measures with the traditional methods of backward linkages. We find that the network-based measures such as PageRank centrality and community coreness measure can give valuable insights into identifying the key industries

Assortative mating for human height: A meta-analysis

OBJECTIVES: The study of assortative mating for height has a rich history in human biology. Although the positive correlation between the stature of spouses has often been noted in western populations, recent papers suggest that mating patterns for stature are not universal. The objective of this paper was to review the published evidence to examine the strength of and universality in assortative mating for height. METHODS: We conducted an extensive literature review and meta-analysis. We started with published reviews but also searched through secondary databases. Our search led to 154 correlations of height between partners. We classified the populations as western and non-western based on geography. These correlations were then analyzed via meta-analytic techniques. RESULTS: 148 of the correlations for partner heights were positive and the overall analysis indicates moderate positive assortative mating (r = .23). Although assortative mating was slightly stronger in countries that can be described as western compared to non-western, this difference was not statistically significant. We found no evidence for a change in assortative mating for height over time. There was substantial residual heterogeneity in effect sizes and this heterogeneity was most pronounced in western countries. CONCLUSIONS: Positive assortative mating for height exists in human populations, but is modest in magnitude suggesting that height is not a major factor in mate choice. Future research is necessary to understand the underlying causes of the large amount of heterogeneity observed in the degree of assortative mating across human populations, which may stem from a combination of methodological and ecological differences

Efficacy of limonene nano coatings on post-harvest shelf life of strawberries

Strawberries are highly demanded fruits because of their color, nutritional values and appearance. The aim of this study was to develop and characterize alginate and limonene liposomes as edible coating materials and to determine their efficacy in shelf life extension and maintaining quality parameters of ‘Chandler’ strawberries. Alginate solution (1.5% w/v) and Limonene liposomes prepared from 80% lecithin and 20% PDA were used as edible coating materials. Fungal decay percentage, total yeast and mold counts, headspace atmosphere analysis, total soluble solids, pH, titratable acidity, total anthocyanin content and total phenolics were analyzed to assess fruit quality during 14 days at 4 °C of storage. Days of storage was found to be significant in maintaining the quality of the strawberries. Among the coating types, limonene liposomes were found to be significantly more effective in maintaining the lower concentration of carbon dioxide (CO2), lower the change in pH (3.9), and had higher total anthocyanin (43.85) content during storage than those without a liposomal coating. Thus, limonene liposomes were found to be useful for extending the shelf life and maintaining quality of strawberry fruits

Origin and insertion of the medial patellofemoral ligament: a systematic review of anatomy.

PURPOSE: The medial patellofemoral ligament (MPFL) is the major medial soft-tissue stabiliser of the patella, originating from the medial femoral condyle and inserting onto the medial patella. The exact position reported in the literature varies. Understanding the true anatomical origin and insertion of the MPFL is critical to successful reconstruction. The purpose of this systematic review was to determine these locations. METHODS: A systematic search of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed and Cochrane Library) and unpublished literature databases was conducted from their inception to the 3 February 2016. All papers investigating the anatomy of the MPFL were eligible. Methodological quality was assessed using a modified CASP tool. A narrative analysis approach was adopted to synthesise the findings. RESULTS: After screening and review of 2045 papers, a total of 67 studies investigating the relevant anatomy were included. From this, the origin appears to be from an area rather than (as previously reported) a single point on the medial femoral condyle. The weighted average length was 56 mm with an 'hourglass' shape, fanning out at both ligament ends. CONCLUSION: The MPFL is an hourglass-shaped structure running from a triangular space between the adductor tubercle, medial femoral epicondyle and gastrocnemius tubercle and inserts onto the superomedial aspect of the patella. Awareness of anatomy is critical for assessment, anatomical repair and successful surgical patellar stabilisation. LEVEL OF EVIDENCE: Systematic review of anatomical dissections and imaging studies, Level IV

Catching-up in the global factory: analysis and policy implications

MNEs shape the location of activities in the world economy, linking diverse regions in what has been called the global factory. This study portrays the evolution of incomes and employment in the global factory using a quantitative input–output approach. We find emerging economies forging ahead relative to advanced economies in income derived from fabrication activities, handling the physical transformation process of goods. In contrast, convergence in income derived from knowledge-intensive activities carried out in pre- and post-fabrication stages is much slower. We discuss possible barriers to catching-up and policy implications for emerging economies in developing innovation capabilities, stressing the pivotal role of MNEs

Towards evidence-based marketing: The case of childhood obesity

Contentious commodities such as tobacco, alcohol and fatty foods are bringing marketing under scrutiny from consumers and policymakers. Yet there is little agreement on whether marketing is harmful to society. Systematic review (SR), a methodology derived from clinical medicine, offers marketers a tool for providing resolution and allowing policymakers to proceed with greater confidence. This article describes how SR methods were applied for the first time to a marketing problem -- the effects of food promotion to children. The review withstood scrutiny and its findings were formally ratified by government bodies and policymakers, demonstrating that SR methods can transfer from clinical research to marketing

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference