327 research outputs found

    Assassins and apples: the environmental constraints of two snails that threaten Australian aquatic systems

    Get PDF
    Context: Alien freshwater snails pose a substantial risk to Australian native aquatic biota.Aims: This study aims to determine the thermal and salinity ranges of two introduced species within Australia, Pomacea sp. and Anentome sp., to facilitate predictions of their potential geographic range should they become widely established.Methods: Laboratory tests were conducted to assess behavioural responses of snails to altered temperature or salinity after different acclimation regimes.Key results: After acclimation at 25°C, Pomacea sp. had a median activity range of 13.5–38°C and Anentome sp. of 12–38.5°C. Higher acclimation temperatures produced observable effects, whereas lower acclimation temperatures did not. Salinity tolerances differed, with Pomacea sp. remaining active at up to 8 parts per thousand (ppt) (after acclimation at 25°C), with acclimation at 20°C resulting in a lower salinity tolerance. By contrast, Anentome sp. snails were active at up to 5 ppt after low salinity acclimation, demonstrating enhanced salinity tolerance compared with non-salinity acclimations.Conclusions: These results showed that both snails are capable of surviving temperatures and salinities that would allow invasion into subtropical and warm-temperate Australian aquatic systems.Implications: Free from the constraints of natural predators, competitors, and parasites, these snails should be of great concern to biosecurity agencies in Australia

    Simulation of actively controlled spacecraft with flexible appendages

    Full text link
    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76688/1/AIAA-25388-716.pd

    Deletion Study of DNA Topoisomerase IB from Leishmania donovani: Searching for a Minimal Functional Heterodimer

    Get PDF
    The substantial differences between trypanosomal and leishmanial DNA topoisomerase IB concerning to their homologues in mammals have provided a new lead in the study of the structural determinants that can be effectively targeted. Leishmania donovani, the causative agent of visceral leishmaniasis, contains an unusual heterodimeric DNA topoisomerase IB. The catalytically active enzyme consists of a large subunit (LdTopIL), which contains the non-conserved N-terminal end and the phylogenetically conserved “core” domain, and of a small subunit (LdTopIS) which harbors the C-terminal region with the characteristic tyrosine residue in the active site. Heterologous co-expression of LdTopIL and LdTopIS genes in a topoisomerase I deficient yeast strain, reconstitutes a fully functional enzyme LdTopIL/S which can be used for structural studies. An approach by combinatorial cloning of deleted genes encoding for truncated versions of both subunits was used in order to find out structural insights involved in enzyme activity or protein-protein interaction. The role played by the non-conserved N-terminal extension of LdTopIL in both relaxation activity and CPT sensitivity has been examined co-expressing the full-length LdTopIS and a fully active LdTopIΔS deletion with several deletions of LdTopIL lacking growing sequences of the N-terminal end. The sequential deletion study shows that the first 26 amino acids placed at the N-terminal end and a variable region comprised between Ala548 to end of the C-terminal extension of LdTopIL were enzymatically dispensable. Altogether this combinatorial approach provides important structural insights of the regions involved in relaxation activity and for understanding the atypical structure of this heterodimeric enzyme

    The use of oxygen hoods in patients failing on conventional high-flow oxygen delivery systems, the effects on oxygenation, mechanical ventilation and mortality rates in hypoxic patients with COVID-19. A Prospective Controlled Cohort Study

    Get PDF
    © 2021 Introduction: Efforts to meet increased oxygen demands in COVID-19 patients are a priority in averting mechanical ventilation (MV), associated with high mortality approaching 76.4–97.2%. Novel methods of oxygen delivery could mitigate that risk. Oxygen hoods/helmets may improve: O2-saturation (SaO2), reduce in-hospital mechanical ventilation and mortality rates, and reduce length of hospitalization in hypoxic Covid-19 patients failing on conventional high-flow oxygen delivery systems. Methods: DesignProspective Controlled Cohort Study. SettingSingle Center. ParticipantsAll patients admitted with a diagnosis of COVID-19 were reviewed and 136/347 patients met inclusion criteria. Study period3/6/2020 to 5/1/2020. 136 participants completed the study with known status for all outcome measures. Intervention or exposureOxygen hoods/helmets as compared to conventional high-flow oxygen delivery systems. Main outcome(s) and measure(s): 1) Pre and post change in oxygen saturation (SaO2). 2) In-hospital Mechanical Ventilation (MV). 3) In-hospital Mortality. 4) Length of hospitalization. Results: 136 patients including 58-intervention and 78-control patients were studied. Age, gender, and other demographics/prognostic indicators were comparable between cohorts. Oxygen hoods averted imminent or immediate intubation/MV in all 58 COVID-19 patients failing on conventional high-flow oxygen delivery systems with a mean improvement in SaO2 of 8.8%, p \u3c 0.001. MV rates were observed to be higher in the control 37/78 (47.4%) as compared to the intervention cohort 23/58 (39.7%), a difference of 7.7%, a 27% risk reduction, not statistically significant, OR 95%CI 0.73 (0.37–1.5). Mortality rates were observed higher in the control 54/78 (69.2%) as compared to the intervention cohort 36/58 (62.1%), a difference of 7.1%, a 27% risk reduction, not statistically significant OR 95%CI 0.73 (0.36–1.5). Conclusion: Oxygen hoods demonstrate improvement in SaO2 for patients failing on conventional high-flow oxygen-delivery systems and prevented imminent mechanical ventilation. In-hospital mechanical ventilation and mortality rates were reduced with the use of oxygen hoods but not found to be statistically significant. The oxygen hood is a safe, effective oxygen-delivery system which may reduce intubation/MV and mortality rates. Their use should be considered in treating hypoxic COVID-19 patients. Further research is warranted. Trial registration: ClinicalTrials.gov Identifier: NCT 04407260

    Anaesthesia of three young grey seals (Halichoerus grypus) for fracture repair

    Get PDF
    Three young grey seals (Halichoerus grypus) were presented separately for fracture repair to the veterinary teaching hospital of University College Dublin. The seals were premedicated with a combination of pethidine, midazolam and atropine; anaesthesia was induced with propofol via the front flipper vein and maintained with sevoflurane or isoflurane in oxygen. One of the seals did not breathe spontaneously after anaesthesia; a cardiac arrest, resulting in death, occurred after several hours of mechanical ventilation. Post-mortem examination revealed a severe lungworm infestation and parasitic pneumonia in this animal. The two other seals recovered uneventfully from anaesthesia

    The spatial context of clinic-reported sexually transmitted infection in Hong Kong

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The incidence and prevalence of sexually transmitted infection (STI) in China has been on the rise in the past decade. Delineation of epidemiologic pattern is often hampered by its uneven distribution. Spatial distribution is often a neglected aspect of STI research, the description of which may enhance epidemiologic surveillance and inform service development.</p> <p>Methods</p> <p>Over a one month-period, all first time attendees of 6 public STI clinics in Hong Kong were interviewed before clinical consultation using a standard questionnaire to assess their demographic, clinical and behavioural characteristics. A GIS (geographic information system)-based approach was adopted with mapping performed. The cases attending the clinics in different locations were profiled. A comparison was made between neighbourhood cases (patients living near a clinic) and distant cases (those farther off), by calculating the odds ratio for demographic, behavioural and geographic characteristics.</p> <p>Results</p> <p>Of the 1142 STI patients evaluated, the residence locations of 1029 (90.1%) could be geocoded, of which 95.6% were ethnic Chinese and 63.4% male. Geographically only about a quarter lived in the same district as the clinic. STI patients aged 55 or above were more likely to be living in the vicinity of the clinic, located in the same or adjacent tertiary planning unit (a small geographic unit below district level). A majority of patients came from locations a few kilometers from the clinic, the distance of which varies between clinics. Overall, more syphilis cases were reported in patients residing in the same or adjacent tertiary planning unit, while distant cases tended to give a higher risk of inconsistent condom use. There were otherwise no significant clinical and epidemiologic differences between neighbourhood and distant STI cases.</p> <p>Conclusions</p> <p>There was no specific relationship between STI and the residence location of patients as regards their clinical and epidemiologic characteristics in the territory of Hong Kong. Older STI patients were however more inclined to attend the nearby STI clinics. Most patients have travelled a variable distance to access the STI service. The relationship between STI clinic cases and distance could be a complex issue intertwined between psychosocial characteristics and STI service coverage.</p

    Identification of a Novel Topoisomerase Inhibitor Effective in Cells Overexpressing Drug Efflux Transporters

    Get PDF
    BACKGROUND:Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology. METHOD AND FINDINGS:A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo. CONCLUSIONS:The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids

    Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis

    Get PDF

    Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

    Get PDF
    corecore