A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization

Human gammaherpesviruses are associated with the development of lymphomas and epithelial malignancies. The heterogeneity of these tumors reflects the ability of these viruses to route infection to different cell types at various stages of their lifecycle. While the Epstein Barr virus uses gp42 - human leukocyte antigen class II interaction as a switch of cell tropism, the molecular mechanism that orientates tropism of rhadinoviruses is still poorly defined. Here, we used bovine herpesvirus 4 (BoHV-4) to further elucidate how rhadinoviruses regulate their infectivity. In the absence of any gp42 homolog, BoHV-4 exploits the alternative splicing of its Bo10 gene to produce distinct viral populations that behave differently based on the originating cell. While epithelial cells produce virions with high levels of the accessory envelope protein gp180, encoded by a Bo10 spliced product, myeloid cells express reduced levels of gp180. As a consequence, virions grown in epithelial cells are hardly infectious for CD14+ circulating cells, but are relatively resistant to antibody neutralization due to the shielding property of gp180 for vulnerable entry epitopes. In contrast, myeloid virions readily infect CD14+ circulating cells but are easily neutralized. This molecular switch could therefore allow BoHV-4 to promote either, on the one hand, its dissemination into the organism, or, on the other hand, its transmission between hosts

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

Background: Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of “minor impact genes” such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors. Aim: we focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (- 4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911C (Lys751Gln), XPF Arg415Gln, XPG Asp1104His, ERCC1 C118T]; homologous recombination repair [ NBS1 Glu185Gln, Rad51 135G/C, XRCC3 C18067 (Thr241Met)]. Material and methods: The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher’s exact test with a Bonferroni correction for multiple testing was used. Results: We found that: i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391,3.7782) p=0.038], ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215,0,9131) p=0.031] for an individual with at least one A allele at this locus. Conclusions: 1. the XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer. 2. the NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC

Friendship and organization: Learning from the western friendship tradition

This article describes and explores some key concepts from the classical, Western friendship tradition in order to see whether anything may be learned from them about the processes of organizing today. First, it looks at the difference between the modern notion of friendship, which emphasizes intimacy as the basis for an interpersonal relationship, and the classical tradition, which held a much more differentiated view, extending from the interpersonal to the political and systemic. In particular, the idea of friendship as a hexis is described – that is, as a state of mind or disposition towards others rather than just an intimate relationship. Second, it looks at the idea of ‘levels’ of friendship – from those based on utility or pleasure to those rooted in a striving after virtue – which opens up possibilities for analysing the culture of human relationships in organizations. Finally, it examines ways in which these ideas might be applied in organizations through the elaboration of the practices of friendship in the context of levels of friendship and of the idea of friendship as a state of mind. © 2007 Taylor and Francis Group, LLC