An evaluation and comparison of conservation guidelines for an at-risk migratory songbird

For at-risk wildlife species, it is important to consider conservation within the process of adaptive management. Golden-winged Warblers (Vermivora chrysoptera) are Neotropical migratory songbirds that are experiencing long-term population declines due in part to the loss of early-successional nesting habitat. Recently-developed Golden-winged Warbler habitat management guidelines are being implemented by USDA: Natural Resource Conservation Service (2014) and its partners through the Working Lands For Wildlife (WLFW) program. During 2012–2014, we studied the nesting ecology of Golden-winged Warblers in managed habitats of the eastern US that conformed to WLFW conservation practices. We evaluated five NRCS “management scenarios” with respect to nesting success and attainment of recommended nest site vegetation conditions outlined in the Golden-winged Warbler breeding habitat guidelines. Using estimates of territory density, pairing rate, nest survival, and clutch size, we also estimated fledglingproductivity (number of fledglings/ha) for each management scenario. In general, Golden-winged Warbler nest survival declined as each breeding season advanced, but nest survival was similar across management scenarios. Within each management scenario, vegetation variables had little influence on nest survival. Still, percent Rubus cover and density of \u3e2 m tall shrubs were relevant in some management scenarios. All five management scenarios rarely attained recommended levels of nest site vegetation conditions for Golden-winged, yet nest survival was high. Fledgling productivity estimates for each management scenario ranged from 2.1 to 8.6 fledglings/10 hectares. Our results indicate that targeted habitat management for Golden-winged Warblers using a variety of management techniques on private lands has the capability to yield high nest survival and fledgling productivity, and thus have the potential to contribute to the species recovery

Total body irradiation must be delivered at high dose for efficient engraftment and tolerance in a rhesus stem cell gene therapy model

Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) gene therapy applications. However, low gene marking was previously observed in gene therapy trials, suggesting that RIC might be insufficient for (i) opening niches for efficient engraftment and/or (ii) inducing immunological tolerance for transgene-encoded proteins. Therefore, we evaluated both engraftment and tolerance for gene-modified cells using our rhesus HSC gene therapy model following RIC. We investigated a dose de-escalation of total body irradiation (TBI) from our standard dose of 10Gy (10, 8, 6, and 4Gy), in which rhesus CD34+ cells were transduced with a VSVG-pseudotyped chimeric HIV-1 vector encoding enhanced green fluorescent protein (GFP) (or enhanced yellow fluorescent protein (YFP)). At ∼6 months after transplantation, higher-dose TBI resulted in higher gene marking with logarithmic regression in peripheral blood cells. We then evaluated immunological tolerance for gene-modified cells, and found that lower-dose TBI allowed vigorous anti-GFP antibody production with logarithmic regression, while no significant anti-VSVG antibody formation was observed among all TBI groups. These data suggest that higher-dose TBI improves both engraftment and immunological tolerance for gene-modified cells. Additional immunosuppression might be required in RIC to induce tolerance for transgene products. Our findings should be valuable for developing conditioning regimens for HSC gene therapy applications

Diagnostic challenges of prolonged post-treatment clearance of Plasmodium nucleic acids in a pre-transplant autosplenectomized patient with sickle cell disease

Abstract Background Autosplenectomy, as a result of sickle cell disease, is an important risk factor for severe malaria. While molecular methods are helpful in providing rapid and accurate infection detection and species identification, the effect of hyposplenism on result interpretation during the course of infection should be carefully considered. Case presentation A 32-year old autosplenectomized Nigerian male with severe sickle cell disease was referred to the National Institutes of Health for allogenic hematopoietic stem cell transplant. Despite testing negative for malaria by both smear and PCR 2 weeks after arrival in the USA, the patient developed fever and diffuse bilateral lower rib cage and upper abdominal pain 2 weeks later and subsequently tested positive for Plasmodium falciparum. Parasitaemia was tracked over time by microscopy and nucleic acid tests to evaluate the therapeutic response in the setting of hyposplenism. The patient showed prompt resolution of patent infection by microscopy but remained positive by molecular methods for > 30 days after treatment initiation. Conclusion While molecular testing can provide sensitive Plasmodium nucleic acid detection, the persistence of Plasmodium nucleic acids following adequate treatment in functionally asplenic patients can lead to a diagnostic dilemma. In such patients, clinical response and peripheral blood smears should guide patient management following treatment. Nonetheless, in pre-transplant patients at high-risk for pre-existing Plasmodium infections, highly sensitive molecular assays can be useful to rule out infection prior to transplantation