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Abstract Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

A biodiversity survey on three corallivorous snails (Mollusca: Gastropoda) was performed at 28 sites around the island of Bonaire to assess their distribution patterns and associated host corals. The snails and their hosts were identified and counted in three depth zones: 5–10, 10–20, and 20–30 m. The snails were Coralliophila galea and C. salebrosa (Muricidae: Coralliophilinae), and Cyphoma gibbosum (Ovulidae: Simniinae). All three species were widespread around the island without apparent interspecific geographical variation. Coralliophila galea was found exclusively on scleractinian corals, Coralliophila salebrosa almost exclusively on octocorals, and Cyphoma gibbosum only on octocorals. Coralliophila salebrosa showed more dietary overlap with Cyphoma gibbosum than with Coralliophila galea. Coralliophila galea was the most commonly encountered species with the largest number of host species. Owing to its hosts distribution, this species also showed a greater maximum depth and a wider bathymetrical range than the other two snails. The other two snails were shallower and their depth ranges did not differ significantly. Host-coral size did not seem to have influence on the number of snails per host. Coral damage caused by the snails was visible but appeared to be low, causing no mortality in Bonaire, which suggests that the relation with their hosts is more parasitic than predatory. Because these three corallivores have occasionally been reported to occur as outbreaks in other Caribbean localities and may act as vectors in the dispersal of coral diseases, it is recommended that future studies should focus on their population dynamics.

Summary: Inflammatory signaling pathways are tightly regulated to avoid chronic inflammation and the development of disease. OTULIN is a deubiquitinating enzyme that controls inflammation by cleaving linear ubiquitin chains generated by the linear ubiquitin chain assembly complex. Here, we show that ablation of OTULIN in liver parenchymal cells in mice causes severe liver disease which is characterized by liver inflammation, hepatocyte apoptosis, and compensatory hepatocyte proliferation, leading to steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). Genetic ablation of Fas-associated death domain (FADD) completely rescues and knockin expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) significantly protects mice from developing liver disease, demonstrating that apoptosis of OTULIN-deficient hepatocytes triggers disease pathogenesis in this model. Finally, we demonstrate that type I interferons contribute to disease in hepatocyte-specific OTULIN-deficient mice. Our study reveals the critical importance of OTULIN in protecting hepatocytes from death, thereby preventing the development of chronic liver inflammation and HCC. : Hepatocellular carcinoma (HCC) develops as a result of chronic liver inflammation. Verboom et al. identify OTULIN as a critical liver-protective protein, essential in preventing hepatocyte apoptosis, which could trigger compensatory hepatocyte proliferation, chronic liver inflammation, fibrosis, and HCC.

The central nervous system (CNS) has specific barriers that protect the brain from potential threats and tightly regulate molecular transport. Despite the critical functions of the CNS barriers, the mechanisms underlying their development and function are not well understood, and there are very limited experimental models for their study. Claudin 5 is a tight junction protein required for blood brain barrier (BBB) and, probably, choroid plexus (CP) structure and function in vertebrates. Here, we show that the gene claudin 5a is the zebrafish orthologue with high fidelity expression, in the BBB and CP barriers, that demonstrates the conservation of the BBB and CP between humans and zebrafish. Expression of claudin 5a correlates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show that claudin 5a-expressing cells of the CP are ciliated ependymal cells that drive fluid flow in the brain ventricles. Finally, we find that CP development precedes BBB development and that claudin 5a expression occurs simultaneously with angiogenesis. Thus, our novel transgenic zebrafish represents an ideal model to study CNS barrier development and function, critical in understanding the mechanisms underlying CNS barrier function in health and disease.