1,336 research outputs found

    Movements and diving behaviour of white-chinned petrels: Diurnal variation and implications for bycatch mitigation

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    Many seabirds dive to forage, and the ability to use this hunting technique varies according to such factors as morphology, physiology, prey availability, and ambient light levels. Proficient divers are more able to seize sinking baits deployed by longline fishing vessels and may return them to the surface, increasing exposure of other species. Hence, diving ability has major implications for mitigating incidental mortality (bycatch) in fisheries. Here, the diving behaviour and activity patterns of the most bycaught seabird species worldwide, the white-chinned petrel (Procellaria aequinoctialis), tracked from Bird Island (South Georgia), are analysed. Three data sources (dives, spatial movements, and immersion events) are combined to examine diverse aspects of at-sea foraging behaviour, and their implications for alternative approaches to bycatch mitigation are considered. The tracked white-chinned petrels (n = 14) mostly performed shallow dives (<3 m deep) of very short duration (<5 s), predominantly during darkness, but only 7 and 10% of landings in daylight and darkness, respectively, involved diving, suggesting that surface-seizing is the preferred foraging technique. Nonetheless, individuals were able to dive to considerable depth (max = 14.5 m) and at speed (max = 2.0 m·s−1), underlining the importance of using heavy line-weighting to maximize hook sink rates, and bird-scaring lines (Tori lines) that extend for long distances behind vessels to protect hooks until beyond diving depths

    The promoter from SlREO, a highly-expressed, root-specific Solanum lycopersicum gene, directs expression to cortex of mature roots

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    Root-specific promoters are valuable tools for targeting transgene expression, but many of those already described have limitations to their general applicability. We present the expression characteristics of SlREO, a novel gene isolated from tomato (Solanum lycopersicum L.). This gene was highly expressed in roots but had a very low level of expression in aerial plant organs. A 2.4-kb region representing the SlREO promoter sequence was cloned upstream of the uidA GUS reporter gene and shown to direct expression in the root cortex. In mature, glasshouse-grown plants this strict root specificity was maintained. Furthermore, promoter activity was unaffected by dehydration or wounding stress but was somewhat suppressed by exposure to NaCl, salicylic acid and jasmonic acid. The predicted protein sequence of SlREO contains a domain found in enzymes of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. The novel SlREO promoter has properties ideal for applications requiring strong and specific gene expression in the bulk of tomato root tissue growing in soil, and is also likely to be useful in other Solanaceous crop

    Intra-anal imiquimod cream against human papillomavirus infection in men who have sex with men living with hiv: A single-arm, open-label pilot study

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    Men who have sex with men (MSM) living with HIV have a high prevalence and incidence of anal high-risk human papillomavirus (hrHPV) and anal cancer. We conducted an open-label, single-arm pilot study to examine the tolerability of imiquimod cream among MSM aged ≥18 years, living with HIV, who tested positive for anal hrHPV at Melbourne Sexual Health Centre between April 2018 and June 2020. We instructed men to apply 6.25 mg imiquimod intra-anally and peri-anally 3 doses per week for 16 weeks (period 1) and then one dose per week for a further 48 weeks (period 2). Twenty-seven MSM enrolled in period 1 and 24 (86%) applied at least 50% of doses. All men reported adverse events (AEs), including 39.5% grade 1, 39.5% grade 2, and 21% grade 3 AEs on at least one occasion. Eighteen MSM (67%) temporarily stopped using imiquimod during period 1, most commonly due to local AEs (n = 11) such as irritation and itching. Eighteen MSM continued in period 2 and all applied at least 50% of doses with no treatment-limiting AEs reported. Imiquimod 3 doses per week caused local AEs in most men and was not well tolerated. In contrast, once-a-week application was well tolerated over 48-weeks with no treatment-limiting AEs

    Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

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    Evidence supporting the critical role of transforming growth factor β1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the transforming growth factor β1 pathway are presented

    Functional and Structural Insights Revealed by Molecular Dynamics Simulations of an Essential RNA Editing Ligase in Trypanosoma brucei

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    RNA editing ligase 1 (TbREL1) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD) simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme

    Cavity Induced Interfacing of Atoms and Light

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    This chapter introduces cavity-based light-matter quantum interfaces, with a single atom or ion in strong coupling to a high-finesse optical cavity. We discuss the deterministic generation of indistinguishable single photons from these systems; the atom-photon entanglement intractably linked to this process; and the information encoding using spatio-temporal modes within these photons. Furthermore, we show how to establish a time-reversal of the aforementioned emission process to use a coupled atom-cavity system as a quantum memory. Along the line, we also discuss the performance and characterisation of cavity photons in elementary linear-optics arrangements with single beam splitters for quantum-homodyne measurements.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

    Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

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    Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

    Emergency management in health: key issues and challenges in the UK

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    Background Emergency planning in the UK has grown considerably in recent years, galvanised by the threat of terrorism. However, deficiencies in NHS emergency planning were identified and the evidence-base that underpins it is questionable. Inconsistencies in terminologies and concepts also exist. Different models of emergency management exist internationally but the optimal system is unknown. This study examines the evidence-base and evidence requirements for emergency planning in the UK health context. Methods The study involved semi-structured interviews with key stakeholders and opinion leaders. Purposive sampling was used to obtain a breadth of views from various agencies involved in emergency planning and response. Interviews were then analysed using a grounded approach using standard framework analysis techniques. Results We conducted 17 key informant interviews. Interviewees identified greater gaps in operational than technical aspects of emergency planning. Social and behavioural knowledge gaps were highlighted with regards to how individuals and organisations deal with risk and behave in emergencies. Evidence-based approaches to public engagement and for developing community resilience to disasters are lacking. Other gaps included how knowledge was developed and used. Conflicting views with regards to the optimal configuration and operation of the emergency management system were voiced. Conclusions Four thematic categories for future research emerged: (i) Knowledge-base for emergency management: Further exploration is needed of how knowledge is acquired, valued, disseminated, adopted and retained. (ii) Social and behavioural issues: Greater understanding of how individuals approach risk and behave in emergencies is required. (iii) Organisational issues in emergencies: Several conflicting organisational issues were identified; value of planning versus plans, flexible versus standardized procedures, top-down versus bottom-up engagement, generic versus specific planning, and reactive versus proactive approaches to emergencies. (iv) Emergency management system: More study is required of system-wide issues relating to system configuration and operation, public engagement, and how emergency planning is assessed

    Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis

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    Background: A devastating late injury caused by radiation is pulmonary fibrosis. This risk may limit the volume of irradiation and compromise potentially curative therapy. Therefore, development of a therapy to prevent this toxicity can be of great benefit for this patient population. Activation of the chemokine receptor CXCR4 by its ligand stromal cell-derived factor 1 (SDF-1/CXCL12) may be important in the development of radiation-induced pulmonary fibrosis. Here, we tested whether MSX-122, a novel small molecule and partial CXCR4 antagonist, can block development of this fibrotic process. Methodology/Principal Findings: The radiation-induced lung fibrosis model used was C57BL/6 mice irradiated to the entire thorax or right hemithorax to 20 Gy. Our parabiotic model involved joining a transgenic C57BL/6 mouse expressing GFP with a wild-type mouse that was subsequently irradiated to assess for migration of GFP+ bone marrow-derived progenitor cells to the irradiated lung. CXCL12 levels in the bronchoalveolar lavage fluid (BALF) and serum after irradiation were determined by ELISA. CXCR4 and CXCL12 mRNA in the irradiated lung was determined by RNase protection assay. Irradiated mice were treated daily with AMD3100, an established CXCR4 antagonist; MSX-122; and their corresponding vehicles to determine impact of drug treatment on fibrosis development. Fibrosis was assessed by serial CTs and histology. After irradiation, CXCL12 levels increased in BALF and serum with a corresponding rise in CXCR4 mRNA within irradiated lungs consistent with recruitment of a CXCR4+ cell population. Using our parabiotic model, we demonstrated recruitment of CXCR4+ bone marrow-derived mesenchymal stem cells, identified based on marker expression, to irradiated lungs. Finally, irradiated mice that received MSX-122 had significant reductions in development of pulmonary fibrosis while AMD3100 did not significantly suppress this fibrotic process. Conclusions/Significance: CXCR4 inhibition by drugs such as MSX-122 may alleviate potential radiation-induced lung injury, presenting future therapeutic opportunities for patients requiring chest irradiation. © 2013 Shu et al
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