Is there really no place like home? Movement, site fidelity, and survival probability of translocated and resident turtles

Wildlife translocations, the deliberate movement of wild individuals from one part of their distribution to another, are increasingly being used as a conservation tool. Despite the popularity of translocations as a conservation technique, translocations are often not successful as a result of excessive movement, poor release site fidelity, and low survival. This study compares the movement patterns, site fidelity, and survival probability of resident and hard-released musk turtles (Sternotherus odoratus) in a complex of patchy distributed wetlands. Our results are different from most translocation studies as the majority of translocated turtles had movement (minimum convex polygon area, total distance moved, number of wetlands used, and the number of movement shifts between wetlands), release site fidelity, and wetland fidelity patterns that were similar to resident turtles. In addition, the survival probabilities of resident and translocated turtles were both high. We believe the combination of poor overland movement capabilities and the patchy distribution of wetlands surrounded by a strong boundary matrix of terrestrial habitat, potentially increased the costs of leaving the wetland. The high costs of travelling overland to more distant wetlands may have constrained the translocated turtles dispersal from the release site and increased release site fidelity. Our study suggests that hard-release translocations may be an effective conservation method for highly aquatic species unlikely to leave the wetland and travel long overland distances.     

Proton-dependent electron transfer from CuA to heme a and altered EPR spectra in mutants close to heme a of cytochrome oxidase

Eukaryotic cytochrome c oxidase (CcO) and homologous prokaryotic forms of Rhodobacter and Paraccocus differ in the EPR spectrum of heme a. It was noted that a histidine ligand of heme a (H102) is hydrogen bonded to serine in Rhodobacter (S44) and Paraccocus CcOs, in contrast to glycine in the bovine enzyme. Mutation of S44 to glycine shifts the heme a EPR signal from g(z) = 2.82 to 2.86, closer to bovine heme a at 3.03, without modifying other properties. Mutation to aspartate, however, results in an oppositely shifted and split heme a EPR signal of g(z) = 2.72/2.78, accompanied by lower activity and drastically inhibited intrinsic electron transfer from CuA to heme a. This intrinsic rate is biphasic; the proportion that is slow is pH dependent, as is the relative intensity of the two EPR signal components. At pH 8, the heme a EPR signal at 2.72 is most intense, and the electron transfer rate (CuA to heme a) is 10-130 s(-1), compared to wild-type at 90,000 s(-1). At pH 5.5, the signal at 2.78 is intensified, and a biphasic rate is observed, 50% fast (approximately wild type) and 50% slow (90 s(-1)). The data support the prediction that the hydrogen-bonding partner of the histidine ligand of heme a is one determinant of the EPR spectral difference between bovine and bacterial CcO. We further demonstrate that the heme a redox potential can be dramatically altered by a nearby carboxyl, whose protonation leads to a proton-coupled electron transfer process.     

Anti-proliferative effect of cytohesin inhibition in gefitinib-resistant lung cancer cells

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been proven to efficiently inhibit the proliferation of a subset of non small-cell lung cancers (NSCLC). Unfortunately, the majority of NSCLC expressing wild type EGFR is primarily resistant to EGFR-TKI treatment. Here, we show that the proliferation of the gefitinib-resistant NSCLC cell lines H460 and A549 is reduced by the small molecule SecinH3 which indirectly attenuates EGFR activation by inhibition of cytohesins, a class of recently discovered cytoplasmic EGFR activators. SecinH3 and gefitinib showed a synergistic antiproliferative effect, which correlated with a profound inhibition of Akt activation and survivin expression. Treating mice bearing H460 xenografts with SecinH3 showed the antiproliferative and pro-apoptotic effect of SecinH3 in vivo. Our data suggest that targeting the EGFR indirectly by inhibiting its cytoplasmic activators, the cytohesins, has the potential to improve the treatment of primarily EGFR-TKI resistant lung cancers.     

The Fifth Domain of Beta 2 Glycoprotein I Protects from Natural IgM Mediated Cardiac Ischaemia Reperfusion Injury

Reperfusion after a period of ischemia results in reperfusion injury (IRI) which involves activation of the inflammatory cascade. In cardiac IRI, IgM natural antibodies (NAb) play a prominent role through binding to altered neoepitopes expressed on damaged cells. Beta 2 Glycoprotein I (β2GPI) is a plasma protein that binds to neoepitopes on damaged cells including anionic phospholipids through its highly conserved Domain V. Domain I of β2GPI binds circulating IgM NAbs and may provide a link between the innate immune system, IgM NAb binding and cardiac IRI. This study was undertaken to investigate the role of Β2GPI and its Domain V in cardiac IRI using wild-type (WT), Rag-1 ^-/- and β2GPI deficient mice. Compared with control, treatment with Domain V prior to cardiac IRI prevented binding of endogenous β2GPI to post-ischemic myocardium and resulted in smaller myocardial infarction size in both WT and β2GPI deficient mice. Domain V treatment in WT mice also resulted in less neutrophil infiltration, less apoptosis and improved ejection fraction at 24 h. Rag-1 -/- antibody deficient mice reconstituted with IgM NAbs confirmed that Domain V prevented IgM NAb induced cardiac IRI. Domain V remained equally effective when delivered at the time of reperfusion which has therapeutic clinical relevance.Based upon this study Domain V may function as a universal inhibitor of IgM NAb binding in the setting of cardiac IRI, which offers promise as a new therapeutic strategy in the treatment of cardiac IRI.     

In vivo transgenic mutation assays

Transgenic rodent gene-mutation models provide relatively quick and statistically reliable assays for gene mutations in the DNA from any tissue. This report summarizes those issues that have been agreed upon at a previous IWGT meeting [Environ. Mol. Mutagen. 35 (2000) 253], and discusses in depth those issues for which no consensus was reached before. It was previously agreed that for regulatory applications, assays should be based upon neutral genes, be generally available in several laboratories, and be readily transferable. For phage-based assays, five to ten animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of approximately 3x10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (pfu or cfu) per tissue per animal. A full set of data should be generated for a vehicle control and two dose groups. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a blocked design, where samples from negative control, positive control and each treatment group are processed together. The total number of pfus or cfus and the MF for each tissue and animal are reported. Statistical tests should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is a statistically non-significant change, with all mean MFs within two standard deviations of the control. During the current workshop, a general protocol was agreed in which animals are treated daily for 28 consecutive days and tissues sampled 3 days after the final treatment. This recommendation could be modified by reducing or increasing the number of treatments or the length of the treatment period, when scientifically justified. Normally male animals alone are sufficient and normally at least one rapidly proliferating and one slowly proliferating tissue should be sampled. Although, as agreed previously, sequencing data are not normally required, they might provide useful additional information in specific circumstances, mainly to identify and correct for clonal expansion and in some cases to determine a mechanism associated with a positive response.     

Continuous bioprocessing: The real thing this time?: 10th Annual bioProcessUK Conference,December 3–4, 2013, London,UK

The Annual bioProcessUK Conference has acted as the key networking event for bioprocess scientists and engineers in the UK for the past 10 years. The following article is a report from the sessions that focused on continuous bioprocessing during the 10^th Annual bioProcessUK Conference (London, December 2013). These sessions were organized by the ‘EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies’ hosted at University College London. A plenary lecture and workshop provided a forum for participants to debate topical issues in roundtable discussions with industry and academic experts from institutions such as Genzyme, Janssen, Novo Nordisk, Pfizer, Merck, GE Healthcare and University College London. The aim of these particular sessions was to understand better the challenges and opportunities for continuous bioprocessing in the bioprocessing sector.     

Environmental NGOs,dispossession, and the state: The ideology and praxis of African nature and development

Zimbabwe provides a significant context to examine the interplay of the new development rhetoric, the actions of powerful conservation organizations, donor policies, a relatively strong and stable government, and the empowerment of local communities. This interplay exists in diverse rural areas where the Communal Areas Management Program for Indigenous Resources (CAMPFIRE) is in various stages of experimentation and implementation. CAMPFIRE has been described as a philosophy of sustainable rural development that enables rural communities to manage, and benefit directly form indigenous wildlife. It is the best known of African efforts to permit African communities to re- assert their management of selected natural resources. The program has the official support of the Zimbabwean government. Nonetheless, there are many potential areas of serious conflict. Three case studies are utilized to explore how the challenges of repossession of critical environmental resources by marginalized communities in the changing context of state and NGO relationships where international tourism is a revenue generator for both the private sector and government.     

Compositional Discrimination of Decompression and Decomposition Gas Bubbles in Bycaught Seals and Dolphins

Gas bubbles in marine mammals entangled and drowned in gillnets have been previously described by computed tomography, gross examination and histopathology. The absence of bacteria or autolytic changes in the tissues of those animals suggested that the gas was produced peri- or post-mortem by a fast decompression, probably by quickly hauling animals entangled in the net at depth to the surface. Gas composition analysis and gas scoring are two new diagnostic tools available to distinguish gas embolisms from putrefaction gases. With this goal, these methods have been successfully applied to pathological studies of marine mammals. In this study, we characterized the flux and composition of the gas bubbles from bycaught marine mammals in anchored sink gillnets and bottom otter trawls. We compared these data with marine mammals stranded on Cape Cod, MA, USA. Fresh animals or with moderate decomposition (decomposition scores of 2 and 3) were prioritized. Results showed that bycaught animals presented with significantly higher gas scores than stranded animals. Gas composition analyses indicate that gas was formed by decompression, confirming the decompression hypothesis.