The first occurrence of the Ponto-Caspian invader, Hemimysis anomala G.O. sars, 1907 (Mysidacea) in the UK

An invasive Ponto-Caspian mysid, Hemimysis anomala G.O. Sars, 1907, was recorded in England for the first time in 2004. Usually a deep water species, in England H. anomala has been observed in shallow waters, in which it shelters under or within anthropogenic structures during daylight. This behaviour renders traditional, net-based survey methods ineffective. Therefore, a distribution survey of the English East Midlands was conducted by searching for individuals by torchlight after dark. H. anomala was found to be widespread within the study area, occurring at 24 out of 51 sites surveyed. However, the geographical limits of its distribution were not determined. The species occurred at low densities in canals and in backwaters of the River Trent, whilst dense swarms were observed in September 2005 in a regatta lake connected to the River Trent. H. anomala has the potential to spread through England's canal network and could colonize the lower reaches and estuaries of rivers including the River Thames and River Severn. Habitat preference analysis indicated that flowing water and absence of shelter prevented population establishment, although the species' U.K. distribution suggests that it can migrate through such areas of unsuitable habitat

High Level of Perforin Expression Is Required for Effective Correction of Hemophagocytic Lymphohistiocytosis

Perforin-1 mutations result in a potentially fatal hemophagocytic lymphohistiocytosis (HLH) with heightened immune activation, hypercytokinemia, pancytopenia, and end-organ damage. At present, hematopoietic stem cell (HSC) transplantation is curative, but limited by donor availability and associated mortality, making gene therapy an attractive alternative approach for HLH. We reported that perforin expression driven by cellular promoters in lentiviral (LV) vectors resulted in significant, albeit partial, correction of the inflammatory features in a murine model of HLH. We hypothesized that the level of perforin expression achieved per cell from ectopic moderate-strength cellular promoters (phosphoglycerate kinase gene/perforin-1 gene) is inadequate and thus engineered an LV vector using a viral promoter (MND; a modified Moloney murine leukemia virus long terminal repeat with myeloproliferative sarcoma virus enhancer) containing microRNA126 target sequences to restrict perforin expression in HSCs. We show here that the MND-LV vector restored perforin expression to normal levels in a perforin-deficient human natural killer cell line and perforin gene-corrected Perforin1(-/-) transplant recipients, whereas cellular promoters drove only partial correction. On lymphocytic choriomeningitis virus challenge, the clinical scores and survival improved only with the MND-LV vector, but inflammatory markers and cytotoxicity were improved with all LV vectors. Our studies suggest that although moderate levels of expression can result in partial amelioration of the HLH phenotype, high levels of perforin expression per cell are required for complete correction of HLH