CD40L is selectively expressed on platelets from thrombocytopenic septic patients

Introduction It has been recently hypothesized that septic microangio- pathy is caused or at least promoted by the interaction between endo- thelial surface receptor CD40 and its ligand CD40L, expressed by activated platelets. This interaction produces procoagulative changes in endothelial cells, endothelial apoptosis, subendothelial matrix exposition and microthrombi formation. Since virtually all septic patients show a certain degree of coagulation abnormalities, we hypothesized that low platelet count is associated with a diff erent degree of CD40L expression and that this could correlate with the severity of disease. Methods To determine the infl uence of sepsis on levels of platelet-derived CD40L expression, we performed a prospective observational study in a polyvalent university hospital ICU. Eighteen consecutively septic patients were enrolled in the study, independently of the platelet count and the severity of disease (SOFA score). Flow cytometry of fresh blood from septic patients (n = 18) and age-matched controls (n = 8) was performed for membrane-bound CD40L and CD62P on circulating platelets. Results Flow cytometry demonstrated low levels of CD62P in controls while the levels in patients were high. CD40L+ platelets were selectively found from patients with thrombocytopenia (platelet count ≤60,000/mm3). Furthermore a direct correlation between CD40L expression and the SOFA score was found in patients with sepsis and thrombocytopenia compared to patients with sepsis without thrombocytopenia. Conclusions These results suggest that CD40L expression on platelets is somehow related to the degree of thrombocytopenia and possibly can be a marker of the severity of sepsis. Although the role of endothelial- derived CD40/platelet-derived CD40L interaction is not fully understood during sepsis, the expression of CD40L on platelets could be related to the severity of organ disease due to the possible bursting of endothelial damage through this pathway. Further investigation is needed to determine whether platelets CD40L contributes to endothelial and subsequent organ damage, its role in thrombocytopenia and its correlation with the outcome of sepsis. The microvascular injury seems to be a central event in sepsis, so understanding the mechanisms underlying its development is crucial for the individuation of new and specifi c therapeutic strategies

An Internal Ribosome Entry Site Directs Translation of the 39-Gene from Pelargonium Flower Break Virus Genomic RNA: Implications for Infectivity

[EN] Pelargonium flower break virus (PFBV, genus Carmovirus) has a single-stranded positive-sense genomic RNA (gRNA) which contains five ORFs. The two 59-proximal ORFs encode the replicases, two internal ORFs encode movement proteins, and the 39-proximal ORF encodes a polypeptide (p37) which plays a dual role as capsid protein and as suppressor of RNA silencing. Like other members of family Tombusviridae, carmoviruses express ORFs that are not 59-proximal from subgenomic RNAs. However, in one case, corresponding to Hisbiscus chlorotic ringspot virus, it has been reported that the 39-proximal gene can be translated from the gRNA through an internal ribosome entry site (IRES). Here we show that PFBV also holds an IRES that mediates production of p37 from the gRNA, raising the question of whether this translation strategy may be conserved in the genus. The PFBV IRES was functional both in vitro and in vivo and either in the viral context or when inserted into synthetic bicistronic constructs. Through deletion and mutagenesis studies we have found that the IRES is contained within a 80 nt segment and have identified some structural traits that influence IRES function. Interestingly, mutations that diminish IRES activity strongly reduced the infectivity of the virus while the progress of the infection was favoured by mutations potentiating such activity. These results support the biological significance of the IRES-driven p37 translation and suggest that production of the silencing suppressor from the gRNA might allow the virus to early counteract the defence response of the host, thus facilitating pathogen multiplication and spread.This research was supported by grants BFU2006-11230 and BFU2009-11699 from the Spanish Ministerio de Ciencia e Innovacion (MICINN) and by grants ACOM/2006/210 and ACOMP/2009/040 (to CH) and GVPRE/2008/121 (to OF-M) from the Generalitat Valenciana. The latter was the recipient of an I3P postdoctoral contract from the Spanish Consejo Superior de Investigaciones Cientificas and an additional contract from MICINN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fernandez Miragall, O.; Hernandez Fort, C. (2011). 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The illusion of righteousness: corporate social responsibility practices of the alcohol industry

BACKGROUND: Corporate social responsibility (CSR) has become an integral element of how the alcohol industry promotes itself. The existing analyses of CSR in the alcohol industry point to the misleading nature of these CSR practices. Yet, research has been relatively sparse on how the alcohol industry advances CSR in an attempt to facilitate underlying business interests, and in what ways the ongoing display of industry CSR impacts public health. This paper aims to investigate the alcohol industry’s recent CSR engagements and explain how CSR forms part of the industry’s wider political and corporate strategies. METHODS: Our study used qualitative methods to collect and analyse data. We searched for materials pertaining to CSR activities from websites of three transnational alcohol corporations, social media platforms, media reports and other sources. Relevant documents were thematically analysed with an iterative approach. RESULTS: Our analysis identified three CSR tactics employed by the alcohol companies which are closely tied in with the industry’s underlying corporate intents. First, the alcohol manufacturers employ CSR as a means to frame issues, define problems and guide policy debates. In doing this, the alcohol companies are able to deflect and shift the blame from those who manufacture and promote alcoholic products to those who consume them. Second, the alcohol corporations promote CSR initiatives on voluntary regulation in order to delay and offset alcohol control legislation. Third, the alcohol corporations undertake philanthropic sponsorships as a means of indirect brand marketing as well as gaining preferential access to emerging alcohol markets. CONCLUSIONS: The increasing penetration and involvement of the alcohol industry into CSR highlights the urgent needs for public health counter actions. Implementation of any alcohol control measures should include banning or restricting the publicity efforts of the industry’s CSR and informing the public of the alcohol industry’s notion of social responsibility. More significantly, an internationally binding instrument should be called for to enable countries to differentiate between genuine concerns and spurious altruism, and in doing so, resist the industry’s attempt to erode alcohol control