Population genetics of the frog-killing fungus Batrachochytrium dendrobatidis

Global amphibian decline by chytridiomycosis is a major environmental disaster that has been attributed to either recent fungal spread or environmental change that promotes disease. Here, we present a population genetic comparison of Batrachochytrium dendrobatidis isolates from an intensively studied region of frog decline, the Sierra Nevada of California. In support of a novel pathogen, we find low diversity, no amphibian-host specificity, little correlation between fungal genotype and geography, local frog extirpation by a single fungal genotype, and evidence of human-assisted fungus migration. In support of endemism, at a local scale, we find some diverse, recombining populations. Therefore neither epidemic spread nor endemism alone explains this particular amphibian decline. Recombination raises the possibility of resistant sporangia and a mechanism for rapid spread as well as persistence that could greatly complicate global control of the pathogen.

TLR 9 Activation in Dendritic Cells Enhances Salmonella Killing and Antigen Presentation via Involvement of the Reactive Oxygen Species

Synthetic CpG containing oligodeoxynucleotide Toll like receptor-9 agonist (CpG DNA) activates innate immunity and can stimulate antigen presentation against numerous intracellular pathogens. It was observed that Salmonella Typhimurium growth can be inhibited by the CpG DNA treatment in the murine dendritic cells. This inhibitory effect was mediated by an increased reactive oxygen species production. In addition, it was noted that CpG DNA treatment of dendritic cells during Salmonella infection leads to an increased antigen presentation. Further this increased antigen presentation was dependent on the enhanced reactive oxygen species production elicited by Toll like receptor-9 activation. With the help of an exogenous antigen it was shown that Salmonella antigen could also be cross-presented in a better way by CpG induction. These data collectively indicate that CpG DNA enhance the ability of murine dendritic cells to contain the growth of virulent Salmonella through reactive oxygen species dependent killing.

Intention and Causation in Medical Non-Killing: The impact of criminal law concepts on euthanasia and assisted suicide

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A comparison of the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells.

One of the important temporal stages of radiation action in cellular systems is the chemical phase, where oxygen fixation reactions compete with chemical repair reactions involving reducing agents such as GSH. Using the gas explosion technique it is possible to follow the kinetics of these fast (> 1 ms) reactions in intact cells. We have compared the chemical repair kinetics of the oxygen-dependent free radical precursors leading to DNA single-strand and double-strand breaks, measured using filter elution techniques, with those leading to cell killing in V79 cells. The chemical repair rates for DNA dsb (670s-1 at pH 7.2 and 380s-1 at pH 9.6) and cell killing (530s-1) were similar. This is in agreement with the important role of DNA dsb in radiation induced cell lethality. The rate for DNA ssb precursors was significantly slower (210s-1). The difference in rate between DNA ssb and dsb precursors may be explained on the basis of a dsb free radical precursor consisting of a paired radical, one radical on each strand. The instantaneous probability of one or other of these radicals being chemically repaired and not proceeding to form a dsb will be twice that of a ssb radical precursor. This agrees well with the concept of locally multiply damaged sites (LMDS) produced from clusters of ionizations in DNA (Ward 1985).

The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells. I

Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 mumol dm-3; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s-1 to 144 s-1, and for lethal lesion precursors from 533 s-1 to 165 s-1. This is generally consistent with the role of GSH in the repair-fixation model of radiation damage at the critical DNA lesions. However, the reduction in chemical repair rate was not proportional to the severe thiol depletion (down to almost-equal-to 1% for GSH) and a residual repair capacity remained (almost-equal-to 30%). This was found not to be due to compartmentalization of residual GSH in the nucleus, as the repair rate for dsb precursors in isolated nuclei, washed virtually free of GSH, was identical to that found in GSH-depleted cells (144 s-1), also the OER remained substantially above unity. This suggests that other reducing agents may have a role to play in the chemical repair of oxygen-dependent damage. One possible candidate is the significant level of protein sulphydryls present in isolated nuclei.

HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing

HIV upregulates cell-surface expression of specific ligands for the activating NKG2D receptor, including ULBP-1, -2, -3, but not MICA or MICB, in infected cells both in vitro and in vivo. However, the viral factor(s) involved in NKG2D ligand expression still remains undefined. HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G2 cell-cycle arrest, conditions known to upregulate NKG2D ligands. We report here that HIV-1 selectively induces cell-surface expression of ULBP-2 in primary CD4+ T-lymphocytes by a process that is Vpr-dependent. Importantly, Vpr enhanced the susceptibility of HIV-1-infected cells to NK cell-mediated killing. Strikingly, Vpr alone was sufficient to upregulate expression of all NKG2D ligands and thus promoted efficient NKG2D-dependent NK cell-mediated killing. Delivery of virion-associated Vpr via defective HIV-1 particles induced analogous biological effects in non-infected target cells, suggesting that Vpr may act similarly beyond infected cells. All these activities relied on Vpr ability to activate the ATR-mediated DNA damage/stress checkpoint. Overall, these results indicate that Vpr is a key determinant responsible for HIV-1-induced upregulation of NKG2D ligands and further suggest an immunomodulatory role for Vpr that may not only contribute to HIV-1-induced CD4+ T-lymphocyte depletion but may also take part in HIV-1-induced NK cell dysfunction.

Global trends and factors associated with the illegal killing of elephants: a hierarchical bayesian analysis of carcass encounter data

Elephant poaching and the ivory trade remain high on the agenda at meetings of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Well-informed debates require robust estimates of trends, the spatial distribution of poaching, and drivers of poaching. We present an analysis of trends and drivers of an indicator of elephant poaching of all elephant species. The site-based monitoring system known as Monitoring the Illegal Killing of Elephants (MIKE), set up by the 10th Conference of the Parties of CITES in 1997, produces carcass encounter data reported mainly by anti-poaching patrols. Data analyzed were site by year totals of 6,337 carcasses from 66 sites in Africa and Asia from 2002–2009. Analysis of these observational data is a serious challenge to traditional statistical methods because of the opportunistic and non-random nature of patrols, and the heterogeneity across sites. Adopting a Bayesian hierarchical modeling approach, we used the proportion of carcasses that were illegally killed (PIKE) as a poaching index, to estimate the trend and the effects of site- and country-level factors associated with poaching. Important drivers of illegal killing that emerged at country level were poor governance and low levels of human development, and at site level, forest cover and area of the site in regions where human population density is low. After a drop from 2002, PIKE remained fairly constant from 2003 until 2006, after which it increased until 2008. The results for 2009 indicate a decline. Sites with PIKE ranging from the lowest to the highest were identified. The results of the analysis provide a sound information base for scientific evidence-based decision making in the CITES process.

Can we civilize the Aborigines without killing them? : Florence Nightingale's influence on Bishop Salvado

In 1859 English public health nurse Florence Nightingale decided to conduct a study of the mortality rates in ‘native schools’ in Britain’s colonies. Since the 1837 publication of the House of Commons Report on the impact of British settlement on native people’s, there had been a speculative discourse about the decline of the Aboriginal populations in the colonies; concerns about Aboriginal health and welfare were debated frequently. New Norcia was included in Nightingale’s study and played a big part in Nightingale’s conclusions.
This paper will discuss the study and New Norcia’s participation in it, with particular attention to the correspondence, questionnaires and reports that travelled between Salvado and Nightingale. This unique archive reveals not only Nightingale’s concern about the relationship between civilizing and Aboriginal ill-health in the colonies, but also shed’s light on Salvado’s remarkable insight into this delicate and fraught relationship. By analysing Salvado’s statistical collections and reports for Nightingale’s study on New Norcia’s Aboriginal residents, it is possible to understand that Salvado evaluated and repudiated the influential theory that the Aborigines were inevitably a dying race.

Defacing the acquisitions: a museal-analysis of serial killing horror in cinema

Explores the relationship between serial killing and affect as a form of cinematic horror that repositions the viewer away from the logic of reason through a dismantling of subjectivity via 'modifications' to the body. The chapter has a particular attention to the representation of serial killing in the museum space - theoretically a locus of modern rationality and order- to argue that the museum can be philsophically understood as functioning to detatch desire from subjective formation and fixed encoding of identies. The chapter draws on philosopher Gilles Deleuze and theorists Anna Powell and Steven Shaviro.