Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways

Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naive populations. Despite recent advances in understanding pathogenesis, host response to infection remains poorly understood. Here we modelled a total of 162 metabolites across skin and liver tissues of 61 frogs from four populations (three long-exposed and one naive to the fungus) of the Australian alpine tree frog (Litoria verreauxii alpina) throughout a longitudinal exposure experiment involving both infected and negative control individuals. We found that chytridiomycosis dramatically altered the organism-wide metabolism of clinically diseased frogs. Chytridiomycosis caused catastrophic failure of normal homeostatic mechanisms (interruption of biosynthetic and degradation metabolic pathways), and pronounced dysregulation of cellular energy metabolism. Key intermediates of the tricarboxylic acid cycle were markedly depleted, including in particular a-ketoglutarate and glutamate that together constitute a key nutrient pathway for immune processes. This study was the first to apply a non-targeted metabolomics approach to a fungal wildlife disease and specifically to dissect the host-pathogen interface of Bd-infected frogs. The patterns of metabolite accumulation we have identified reveal whole-body metabolic dysfunction induced by a fungal skin infection, and these findings have broad relevance for other fungal diseases

Towards W b bbar + j at NLO with an automatized approach to one-loop computations

We present results for the O(alpha_s) virtual corrections to q g -> W b bbar q' obtained with a new automatized approach to the evaluation of one-loop amplitudes in terms of Feynman diagrams. Together with the O(alpha_s) corrections to q q' -> W b bbar g, which can be obtained from our results by crossing symmetry, this represents the bulk of the next-to-leading order virtual QCD corrections to W b bbar + j and W b + j hadronic production, calculated in a fixed-flavor scheme with four light flavors. Furthermore, these corrections represent a well defined and independent subset of the 1-loop amplitudes needed for the NNLO calculation of W b bbar. Our approach was tested against several existing results for NLO amplitudes including selected O(alpha_s) one-loop corrections to W + 3 j hadronic production. We discuss the efficiency of our method both with respect to evaluation time and numerical stability.Comment: 14 pages, 3 figure

The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells

The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells

Analysis of the giant genomes of Fritillaria (Liliaceae) indicates that a lack of DNA removal characterizes extreme expansions in genome size.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Plants exhibit an extraordinary range of genome sizes, varying by > 2000-fold between the smallest and largest recorded values. In the absence of polyploidy, changes in the amount of repetitive DNA (transposable elements and tandem repeats) are primarily responsible for genome size differences between species. However, there is ongoing debate regarding the relative importance of amplification of repetitive DNA versus its deletion in governing genome size. Using data from 454 sequencing, we analysed the most repetitive fraction of some of the largest known genomes for diploid plant species, from members of Fritillaria. We revealed that genomic expansion has not resulted from the recent massive amplification of just a handful of repeat families, as shown in species with smaller genomes. Instead, the bulk of these immense genomes is composed of highly heterogeneous, relatively low-abundance repeat-derived DNA, supporting a scenario where amplified repeats continually accumulate due to infrequent DNA removal. Our results indicate that a lack of deletion and low turnover of repetitive DNA are major contributors to the evolution of extremely large genomes and show that their size cannot simply be accounted for by the activity of a small number of high-abundance repeat families.Thiswork was supported by the Natural Environment ResearchCouncil (grant no. NE/G017 24/1), the Czech Science Fou nda-tion (grant no. P501/12/G090), the AVCR (grant no.RVO:60077344) and a Beatriu de Pinos postdoctoral fellowshipto J.P. (grant no. 2011-A-00292; Catalan Government-E.U. 7thF.P.)

Review of the Amphibian Immune Response to Chytridiomycosis, and Future Directions

The fungal skin disease, chytridiomycosis (caused by Batrachochytrium dendrobatidis and B. salamandrivorans), has caused amphibian declines and extinctions globally since its emergence. Characterizing the host immune response to chytridiomycosis has been a focus of study with the aim of disease mitigation. However, many aspects of the innate and adaptive arms of this response are still poorly understood, likely due to the wide range of species' responses to infection. In this paper we provide an overview of expected immunological responses (with inference based on amphibian and mammalian immunology), together with a synthesis of current knowledge about these responses for the amphibian-chytridiomycosis system. We structure our review around four key immune stages: (1) the naïve immunocompetent state, (2) immune defenses that are always present (constitutive defenses), (3) mechanisms for recognition of a pathogen threat and innate immune defenses, and (4) adaptive immune responses. We also evaluate the current hot topics of immunosuppression and immunopathology in chytridiomycosis, and discuss their respective roles in pathogenesis. Our synthesis reveals that susceptibility to chytridiomycosis is likely to be multifactorial. Susceptible amphibians appear to have ineffective constitutive and innate defenses, and a late-stage response characterized by immunopathology and Bd-induced suppression of lymphocyte responses. Overall, we identify substantial gaps in current knowledge, particularly concerning the entire innate immune response (mechanisms of initial pathogen detection and possible immunoevasion by Bd, degree of activation and efficacy of the innate immune response, the unexpected absence of innate leukocyte infiltration, and the cause and role of late-stage immunopathology in pathogenesis). There are also gaps concerning most of the adaptive immune system (the relative importance of B and T cell responses for pathogen clearance, the capacity and extent of immunological memory, and specific mechanisms of pathogen-induced immunosuppression). Improving our capacity for amphibian immunological research will require selection of an appropriate Bd-susceptible model species, the development of taxon-specific affinity reagents and cell lines for functional assays, and the application of a suite of conventional and emerging immunological methods. Despite current knowledge gaps, immunological research remains a promising avenue for amphibian conservation management

Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

The political process of constructing a sustainable London Olympics sports development legacy

This study attempts to develop a research agenda for understanding the process of constructing a sustainable Olympic sports development legacy. The research uses a social constructivist perspective to examine the link between the 2012 London Olympic Games and sustainable sports development. The first part of the paper provides justification for the study of sport policy processes using a constructivist lens. This is followed by a section which critically unpacks sustainable sports development drawing on Mosse’s (1998) ideas of process-oriented research and Searle’s conceptualisation of the construction of social reality. Searle’s (1995) concepts of the assignment of function, collective intentionality, collective rules, and human capacity to cope with the environment are considered in relation to the events and discourses emerging from the legacy vision(s) associated with the 2012 London Olympic Games. The paper concludes by proposing a framework for engaging in process oriented research and highlights key elements, research questions, and methodological issues. The proposed constructivist approach can be used to inform policy, practice, and research on sustainable Olympic sports development legacy

Evolution of resistance to chytridiomycosis is associated with a robust early immune response

Potentiating the evolution of immunity is a promising strategy for addressing biodiversity diseases. Assisted selection for infection resistance may enable the recovery and persistence of amphibians threatened by chytridiomycosis, a devastating fungal skin disease threatening hundreds of species globally. However, knowledge of the mechanisms involved in the natural evolution of immunity to chytridiomycosis is limited. Understanding the mechanisms of such resistance may help speed-assisted selection. Using a transcriptomics approach, we examined gene expression responses of endangered alpine tree frogs (Litoria verreauxii alpina) to subclinical infection, comparing two long-exposed populations with a naïve population. We performed a blinded, randomized and controlled exposure experiment, collecting skin, liver and spleen tissues at 4, 8 and 14\ua0days postexposure from 51 wild-caught captively reared infection-naïve adult frogs for transcriptome assembly and differential gene expression analyses. We analysed our results in conjunction with infection intensity data, and the results of a large clinical survival experiment run concurrently with individuals from the same clutches. Here, we show that frogs from an evolutionarily long-exposed and phenotypically more resistant population of the highly susceptible alpine tree frog demonstrate a more robust innate and adaptive immune response at the critical early subclinical stage of infection when compared with two more susceptible populations. These results are consistent with the occurrence of evolution of resistance against chytridiomycosis, help to explain underlying resistance mechanisms, and provide genes of potential interest and sequence data for future research. We recommend further investigation of cell-mediated immunity pathways, the role of interferons and mechanisms of lymphocyte suppression