424 research outputs found

    Age and sex-selective predation moderate the overall impact of predators

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    © 2014 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society. Acknowledgements: Thanks to J. Reid, S. Redpath, A. Beckerman and an anonymous reviewer for their helpful comments on a previous version of the manuscript. This work was partly funded by a Natural Environment Research Council studentship NE/J500148/1 to SH and a grant NE/F021402/1 to XL and by Natural Research Limited. Forest Research funded all the fieldwork on goshawks, tawny owls and field voles during 1973–1996. We thank B. Little, P. Hotchin, D. Anderson and all field assistants for their help with data collection and Forest Enterprise, T. Dearnley and N. Geddes for allowing and facilitating work in Kielder Forest. In addition, we are grateful to English Nature and the BTO for kindly issuing licences annually visit goshawk nest sites. Data accessibility: All data associated with the study which have not already been given in the text are available from the Dryad Digital Repository: http://doi.org/10.5061/dryad.h1289 (Hoy et al. 2014).Peer reviewedPublisher PD

    Transcription Factor Binding Profiles Reveal Cyclic Expression of Human Protein-coding Genes and Non-coding RNAs

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    Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and a combination of the two types of features can further improve prediction accuracy. We apply our model to a complete list of GENCODE promoters to predict novel cell cycle driving promoters for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that a similar percentage of lincRNAs are cell cycle regulated as protein-coding genes, suggesting the importance of non-coding RNAs in cell cycle division. The model we propose here provides not only a practical tool for identifying novel cell cycle genes with high accuracy, but also new insights on cell cycle regulation by TFs and cis-regulatory elements

    Genetic markers validate using the natural phenotypic characteristics of shed feathers to identify individual northern goshawks Accipiter gentilis

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    Acknowledgements We are grateful to S. Piertney for allowing access to laboratory facilities and to M. Wenzel, R. Ogden and G. Murray-Dickson for their advice on genetic methods. This research was partly funded by a Natural Environment Research Council studentship NE/J500148/1 to SH and by Natural Research Limited.Peer reviewedPublisher PD

    Mitochondrial ROS cause motor deficits induced by synaptic inactivity:implications for synapse pruning

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    Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bugarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS—using mitochondria-targeted Paraquat (MitoPQ)—recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features

    Periplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides

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    This work was supported in part by grants from the Canadian Institutes of Health Research (FDN_148364) (to C.W.). S.D.L. is a recipient of a Natural Science and Engineering Research Council Alexander Graham Bell Canada Graduate Scholarship and Michael Smith Foreign Study Supplement. C.W. is a Canada Research Chair. J.H.N. is a Wellcome Trust Investigator (100209/Z/12/Z).Capsules are surface layers of hydrated capsular polysaccharides (CPSs) produced by many bacteria. The human pathogen Salmonella enterica serovar Typhi produces "Vi antigen" CPS, which contributes to virulence. In a conserved strategy used by bacteria with diverse CPS structures, translocation of Vi antigen to the cell surface is driven by an ATP-binding cassette (ABC) transporter. These transporters are engaged in heterooligomeric complexes proposed to form an enclosed translocation conduit to the cell surface, allowing the transporter to power the entire process. We identified Vi antigen biosynthesis genetic loci in genera of the Burkholderiales, which are paradoxically distinguished from S. Typhi by encoding VexL, a predicted pectate lyase homolog. Biochemical analyses demonstrated that VexL is an unusual metal-independent endolyase with an acidic pH optimum that is specific for Oacetylated Vi antigen. A 1.22-Å crystal structure of the VexL-Vi antigen complex revealed features which distinguish common secreted catabolic pectate lyases from periplasmic VexL, which participates in cell-surface assembly. VexL possesses a right-handed parallel beta-superhelix, of which one face forms an electropositive glycan-binding groove with an extensive hydrogen bonding network that includes Vi antigen acetyl groups and confers substrate specificity. VexL provided a probe to interrogate conserved features of the ABC transporter-dependent export model. When introduced into S. Typhi, VexL localized to the periplasm and degraded Vi antigen. In contrast, a cytosolic derivative had no effect unless export was disrupted. These data provide evidence that CPS assembled in ABC transporter-dependent systems is actually exposed to the periplasm during envelope translocation.Publisher PDFPeer reviewe

    Can invasive Burmese pythons inhabit temperate regions of the southeastern United States?

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    Abstract Understanding potential for range expansion is critical when evaluating the risk posed by invasive species. Burmese pythons (Python molurus bivittatus) are established in southern Florida and pose a significant threat to native ecosystems. Recent studies indicate that climate suitable for the species P. molurus exists throughout much of the southern United States. We examined survivorship, thermal biology, and behavior of Burmese pythons from South Florida in a semi-natural enclosure in South Carolina, where winters are appreciably cooler than in Florida, but within the predicted region of suitable climate. All pythons acclimated to the enclosure, but most died after failing to seek appropriate refugia during sub-freezing weather. The remaining snakes used refugia but died during an unusually cold period in January 2010. Although all snakes died during the study, most survived extended periods at temperatures below those typical of southern Florida and none exhibited obvious signs of disease. Our study represents a first step in evaluating the results of climate matching models and we address factors that may affect range expansion in this invasive species

    Identification of Cell Cycle–Regulated Genes Periodically Expressed in U2OS Cells and their Regulation by FOXM1 and E2F Transcription Factors

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    We identify the cell cycle–regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle–regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle–regulated genes. FOXM1 is bound to cell cycle–regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle–regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle

    Prevalence of pyrazinamide resistance across the spectrum of drug resistant phenotypes of Mycobacterium tuberculosis

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    Pyrazinamide resistance is largely unknown in the spectrum of drug resistant phenotypes. We summarize data on PZA resistance in clinical isolates from South Africa. PZA DST should be performed when considering its inclusion in treatment of patients with rifampicin-resistant TB or MDR-TB

    Live-Cell Monitoring of Periodic Gene Expression in Synchronous Human Cells Identifies Forkhead Genes involved in Cell Cycle Control

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    We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle-dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant

    Diamond photodetectors for next generation 157-nm deep-UV photolithography tools

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    Abstract Next generation photolithography stepper tools will operate at 157 nm and require robust solid state photodetectors to ensure efficient operation and facilitate direct beam monitoring for photoresist exposure dosimetry. There is currently no commercial detector system able to fully meet all the demanding requirements of this application. Diamond, which is intrinsically visible blind and radiation hard, is an obvious candidate for consideration. In this paper we report the results of the first study to assess the viability of thin film polycrystalline diamond photodetectors for use in 157 nm F2-He based laser lithography tools. Co-planar inter-digitated gold photoconductor structures were fabricated on free standing thin film diamond and exposed to pulses from an industrial F2-He laser in the fluence range 0-1.4 mJ cm-2. The electrical and optical characteristics of the devices have been measured and are compared to the response of a standard vacuum photodiode. The suitability of the diamond devices for use at 157 nm is discussed
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