Strategies for the retention of high genetic variability in European flat oyster (<Emphasis Type=Italic>Ostrea edulis</Emphasis>) restoration programmes

The native European flat oyster Ostrea edulis is listed in the OSPAR Convention for the Protection of the Marine Environment of the North-East Atlantic (species and habitat protection) and in the UK Biodiversity Action Plan. Once extremely abundant in the nineteenth century, European stocks of O. edulis have declined during the twentieth century to rare, small, localised populations due to overexploitation, habitat degradation and, most recently, the parasitic disease bonamiosis. Selective breeding programmes for resistance to bonamiosis have been initiated in France and Ireland. High genetic diversity and bonamiosis-resistance would be important features of any sustainable restoration programmes for O. edulis. Oysters were sampled across Europe from four hatchery sources, four pond-cultured sources and four wild, but managed fisheries and were genotyped at five microsatellite loci. Hatchery-produced populations from small numbers of broodstock showed a significant loss of genetic diversity relative to wild populations and pedigree reconstruction revealed that they were each composed of a single large full-sib family and several small full-sib families. This extremely low effective population size highlights the variance in reproductive success among the potential breeders. Pond-cultured oysters were intermediate in genetic diversity and effective population size between hatchery and wild populations. Controlled hatchery production allows the development of bonamiosis-resistant strains, but at the expense of genetic diversity. Large scale pond culture on the other hand can provide a good level of genetic diversity. A mixture of these two approaches is required to ensure a healthy and sustainable restoration programme for O. edulis in Europe.     

Demographic Clusters Identified within the Northern Gulf of Mexico Common Bottlenose Dolphin (Tursiops truncates) Unusual Mortality Event: January 2010 - June 2013

A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana’s record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better discerned by incorporating diagnostic information, including histopathology.     

Human dendritic cells infected with the nonpathogenic Mopeia virus induce stronger T-cell responses than those infected with Lassa virus

The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (APC) may play a crucial role in controlling infection. Here we developed an in vitro model of dendritic-cell (DC)-T-cell coculture in order to characterize human T-cell responses induced by MV- or LV-infected DCs. Our results show very different responses to infection with LV and MV. MV strongly and durably stimulated CD8(+) and CD4(+) T cells, showing early and high activation, a strong proliferative response, and acquisition of effector and memory phenotypes. Furthermore, robust and functional CD4(+) and CD8(+) cytotoxic T lymphocytes (CTL) were generated. LV, however, induced only weak memory responses. Thus, this study allows an improved understanding of the pathogenesis and immune mechanisms involved in the control of human LV.     

APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells

Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the viral protein Vpx coded by members of the SIV(SM)/HIV-2 lineage provides partial protection from APOBEC3A during infection. Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells. The findings presented here open up new venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role of the cellular context in the regulation of the antiviral activities of members of the APOBEC3 family and more generally on the natural functions of APOBEC3A.     

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.Key words: anti-cetuximab antibodies, ELISA, hypersensitivity, therapeutic monoclonal antibody, ROC     

Bread matters: a national initiative to profile the genetic diversity of Australian wheat

The large and complex genome of wheat makes genetic and genomic analysis in this important species both expensive and resource intensive. The application of next-generation sequencing technologies is particularly resource intensive, with at least 17?Gbp of sequence data required to obtain minimal (1×) coverage of the genome. A similar volume of data would represent almost 40× coverage of the rice genome. Progress can be made through the establishment of consortia to produce shared genomic resources. Australian wheat genome researchers, working with Bioplatforms Australia, have collaborated in a national initiative to establish a genetic diversity dataset representing Australian wheat germplasm based on whole genome next-generation sequencing data. Here, we describe the establishment and validation of this resource which can provide a model for broader international initiatives for the analysis of large and complex genomes.     

Passive acoustic monitoring predicts daily variation in North Atlantic right whale presence and relative abundance in Roseway Basin,Canada

North Atlantic right whale monitoring in Roseway Basin, Canada, is primarily based on short‐term (<14 d) visual surveys conducted during August–September. Variability in survey effort has been the biggest limiting factor to studying changes in the population's occurrence and habitat use. Such efforts could be enhanced considerably using passive acoustic monitoring (PAM). We sought to determine if variation in whale presence, relative abundance, demography, and/or behavior (estimated through visual surveys) could be explained by variation in three right whale call types in this habitat. A generalized linear model was fit to 23 d of concurrent PAM and visual monitoring during four summers within the Roseway Basin Right Whale Critical Habitat boundaries. The model revealed significant positive relationships between relative abundance, call counts and presence of surface‐active group behavior. PAM can refine daily right whale presence estimates. While visual observations (n = 23 d) implied a 40% decline in right whale presence during 2014–2015 relative to 2004–2005, PAM data (n = 211 d) showed right whales were present between 71%–85% of survey days throughout all years analyzed. We demonstrate that PAM is a useful tool to extend periods of right whale monitoring, especially in areas where visual monitoring efforts may be limited.