Detection of a gammaretrovirus, XMRV, in the human population: Open questions and implications for xenotransplantation

XMRV (xenotropic murine leukaemia virus-related virus) is a gammaretrovirus that has been detected in human patients with prostate carcinoma, chronic fatigue syndrome (CFS) and also in a small percentage of clinically healthy individuals. It is not yet clear whether the distribution of this virus is primarily limited to the USA or whether it is causally associated with human disease. If future investigations confirm a broad distribution of XMRV and its association with disease, this would have an impact on xenotransplantation of porcine tissues and organs. Xenotransplantation is currently being developed to compensate for the increasing shortage of human material for the treatment of tissue and organ failure but could result in the transmission of porcine pathogens. Maintenance of pathogen-free donor animals will dramatically reduce this risk, but some of the porcine endogenous retroviruses (PERVs) found in the genome of all pigs, can produce infectious virus and infect cultured human cells. PERVs are closely related to XMRV so it is critical to develop tests that discriminate between them. Since recombination can occur between viruses, and recombinants can exhibit synergism, recipients should be tested for XMRV before xenotransplantation

Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment

Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti-type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor a (TNF) in the serum and blister fluid of patients with subepidermal AIBD. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBD. Here we show that in mice, induction of experimental EBA by repeated injections of rabbit anti-mouse type VII collagen antibodies led to increased expression of TNF in skin, as determined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To investigate whether the increased TNF expression is of functional relevance in experimental EBA, we inhibited TNF function using the soluble TNF receptor fusion protein etanercept (Enbrel) or a monoclonal antibody to murine TNF. Interestingly, mice that received either of these treatments showed significantly milder disease progression than controls. In addition, immunohistochemical staining demonstrated reduced numbers of macrophages in lesional skin in mice treated with TNF inhibitors compared with controls. Furthermore, etanercept treatment significantly reduced disease progression in immunization-induced EBA. In conclusion, increased expression of TNF in experimental EBA is of functional relevance, as both the prophylactic blockade of TNF and the therapeutic use of etanercept impaired induction and progression of experimental EBA. Thus, TNF is likely to serve as a new therapeutic target for EBA and AIBDs with a similar pathogenesis

The Restriction of Zoonotic PERV Transmission by Human APOBEC3G

The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections

The Making of Racial and Ethnic Categories: Official Statistics Reconsidered

One of the most striking features of the end of the twentieth century was the resurgence of the ethnic question in public debates, both in developing and in developed countries. Between conflicts and wars interpreted from an ethnic perspective (the Balkans and central Africa), nationalist struggles (the Basque country, Quebec and Belgium), and demands for recognition and political representation by new ethnic minorities resulting from immigration, every country is currently affected by what is commonly known as cultural pluralism (Hobsbawm 1993; Dieckhoff 2000; Faist 2009; Simon and Piché 2013). This ‘ethnic renewal’, to coin the expression used to qualify the growing interest for ethnic diversity in the 1960s in the US, is not only driven by a sort of obsession for cultural differences as an explanation for all kinds of social and political phenomenon. It derives from different legacies: from the increasing diversity of the population of countries that have undergone large immigration flows to the long lasting cohabitation of national minorities within modern Nation states, from the history of slavery to the post-colonial era. This resurgence or extension of the salience of ethnicity in most of the societies around the world can be found not only in public discourses, policy-making, scientific literature and popular representations, but also in the pivotal realm of statistics. Indeed, at the turn of century, an increasing number of countries are processing routinely data on ethnicity or race of their population. This is precisely what this book is about: ethnic and racial classifications in official statistics, as a reflection of the representations of population and an interpretation of social dynamics through different lenses

Pre-bond quality assurance of CFRP surfaces using optically stimulated electron emission

Adhesive bonding reliably contributes to joining carbon fibre reinforced plastics (CFRP). Manufacturing and in-service effects may reduce the mechanical performance of these joints. Their reliability is governed by assuring the surface quality of CFRP material. Roughness of ready-to-bond CFRP surfaces affects in a complex way their wetting behaviour as determined with a water break test. Therefore, further in-line capable techniques are highly desirable for the assessment of surface quality prior to bonding. In the present work, optically stimulated electron emission (OSEE) was investigated with this purpose. Sensitivity and accuracy of OSEE measurements allow to distinguish favourable surface states of CFRP adherends from surface states which are unfavourable for adhesive bonding. We show that OSEE may be applied in field and without electrically contacting CFRP surfaces for sensing moisture, thermal degradation or thin layers of contaminants