Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent

Rewiring carotenoid biosynthesis in plants using a viral vector

[EN] Plants can be engineered to sustainably produce compounds of nutritional, industrial or pharmaceutical relevance. This is, however, a challenging task as extensive regulation of biosynthetic pathways often hampers major metabolic changes. Here we describe the use of a viral vector derived from Tobacco etch virus to express a whole heterologous metabolic pathway that produces the health-promoting carotenoid lycopene in tobacco tissues. The pathway consisted in three enzymes from the soil bacteria Pantoea ananatis. Lycopene is present at undetectable levels in chloroplasts of non-infected leaves. In tissues infected with the viral vector, however, lycopene comprised approximately 10% of the total carotenoid content. Our research further showed that plant viruses that express P. ananatis phytoene synthase (crtB), one of the three enzymes of the heterologous pathway, trigger an accumulation of endogenous carotenoids, which together with a reduction in chlorophylls eventually result in a bright yellow pigmentation of infected tissues in various host-virus combinations. So, besides illustrating the potential of viral vectors for engineering complex metabolic pathways, we also show a yellow carotenoid-based reporter that can be used to visually track infection dynamics of plant viruses either alone or in combination with other visual markers.We thank Veronica Aragones and M. Rosa Rodriguez-Goberna for excellent technical assistance. This research was supported by Spanish Ministerio de Economia y Competitividad (MINECO) grants BIO2014-54269-R to J.-A.D., and BIO2014-59092-P and BIO2015-71703-REDT to M. R.-C. Financial support from the Generalitat Valenciana (PROMETEOII/2014/021), the Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (Ibercarot 112RT0445), and the Generalitat de Catalunya (2014SGR-1434) is also acknowledged. E.M. is the recipient of a pre-doctoral fellowship (AP2012-3751) from the Spanish Ministerio de Educacion, Cultura y Deporte. B.L. is supported by a postdoctoral fellowship (FPDI-2013-018882) from MINECO.Majer, E.; Llorente, B.; Rodríguez-Concepción, M.; Daros Arnau, JA. (2017). Rewiring carotenoid biosynthesis in plants using a viral vector. Scientific Reports. 7. https://doi.org/10.1038/srep41645S7O’Connor, S. E. Engineering of secondary metabolism. Annu. Rev. Genet. 49, 71–94 (2015).Sainsbury, F. & Lomonossoff, G. P. Transient expressions of synthetic biology in plants. Curr. Opin. Plant Biol. 19, 1–7 (2014).Gleba, Y. Y., Tusé, D. & Giritch, A. Plant viral vectors for delivery by Agrobacterium. Curr. Top. Microbiol. 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The Selaginella Genome Identifies Genetic Changes Associated with the Evolution of Vascular Plants

Vascular plants appeared ~410 million years ago then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes (1). We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first non-seed vascular plant genome reported. By comparing gene content in evolutionary diverse taxa, we found that the transition from a gametophyte- to sporophyte- dominated life cycle required far fewer new genes than the transition from a non-seed vascular to a flowering plant, while secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in post- transcriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the tasiRNA pathway and extensive RNA editing of organellar genes

Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study

<p>Abstract</p> <p>Background</p> <p>There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae.</p> <p>Methods</p> <p>We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM.</p> <p>Results</p> <p>Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant.</p> <p>Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM.</p> <p>Conclusions</p> <p>Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women had a higher risk of IM than those of single mothers. Though highly significant, it may nonetheless be a chance finding. We found no evidence that such perinatal factors as birth weight and gestational age, or season of birth, were associated with the risk of hospitalised IM.</p

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie