Neoamphimedine circumvents metnase-enhanced DNA topoisomerase IIα activity through ATP-competitive inhibition

Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC(50) of 0.5 μM. Additionally, we find that the apparent K(m) of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase.     

The importance of comparative phylogeography in diagnosing introduced species: a lesson from the seal salamander, <Emphasis Type="Italic">Desmognathus monticola</Emphasis>

Background  

In most regions of the world human influences on the distribution of flora and fauna predate complete biotic surveys. In some cases this challenges our ability to discriminate native from introduced species. This distinction is particularly critical for isolated populations, because relicts of native species may need to be conserved, whereas introduced species may require immediate eradication. Recently an isolated population of seal salamanders, Desmognathus monticola, was discovered on the Ozark Plateau, ~700 km west of its broad continuous distribution in the Appalachian Mountains of eastern North America. Using Nested Clade Analysis (NCA) we test whether the Ozark isolate results from population fragmentation (a natural relict) or long distance dispersal (a human-mediated introduction).     

品种和栽培条件对草莓果实中水杨酸含量的影响

为了明确草莓内源SA(Salicylic acid,简称SA)含量与其抗病性的关系,并探索人们从草莓等植物性食物中摄取SA的总量,用HPLC分析比较了露地与设施栽培条件下五个对白粉病抗性不同的草莓品种果实的SA含量.结果表明,所测五种草莓红熟期果实内源总SA含量差别明显,露地栽培条件下为1.904～5.023 μg/g,设施栽培条件下为1.068～4.201 μg/g,与各品种的抗白粉病能力无明显相关性.草莓果实中SA均以结合态为主,五个品种结合态SA含量是游离态SA的4～20倍.游离态SA和结合态SA含量都随着果实的成熟而逐渐下降.说明草莓果实中内源SA含量不仅受基因型的影响,并且受栽培环境和成熟度的影响.     

Closing the compliance gap in marine protected areas with human behavioural sciences

Advocates, practitioners and policy-makers continue to use and advocate for marine protected areas (MPAs) to meet global ocean protection targets. Yet many of the worlds MPAs, and especially no-take MPAs, are plagued by poaching and ineffective governance. Using a global dataset on coral reefs as an example, we quantify the potential ecological gains of governing MPAs to increase compliance, which we call the ‘compliance gap’. Using ecological simulations based on model posteriors of joint Bayesian hierarchical models, we demonstrate how increased compliance in no-take MPAs could nearly double target fish biomass (91% increases in median fish biomass), and result in a 292% higher likelihood of encountering top predators. Achieving these gains and closing the compliance gap necessitates a substantial shift in approach and practice to go beyond optimizing enforcement, and towards governing for compliance. This will require engaging and integrating a broad suite of actors, principles, and practices across three key domains: (i)) harnessing social influence, (ii) integrating equity principles, and (iii) aligning incentives through market-based instruments. Empowering and shaping communication between actor groups (e.g., between fishers, practitioners, and policy-makers) using theoretically underpinned approaches from the behavioural sciences is one of the most essential, but often underserved aspects of governing MPAs. We therefore close by highlighting how this cross-cutting tool could be further integrated in governance to bolster high levels of compliance in MPAs.     

Field Validation of the Southern Rock Lobster Paralytic Shellfish Toxin Monitoring Program in Tasmania,Australia

Paralytic shellfish toxins (PST) are found in the hepatopancreas of Southern Rock Lobster Jasus edwardsii from the east coast of Tasmania in association with blooms of the toxic dinoflagellate Alexandrium catenella. Tasmania’s rock lobster fishery is one of the state’s most important wild capture fisheries, supporting a significant commercial industry (AUD 97M) and recreational fishing sector. A comprehensive 8 years of field data collected across multiple sites has allowed continued improvements to the risk management program protecting public health and market access for the Tasmanian lobster fishery. High variability was seen in toxin levels between individuals, sites, months, and years. The highest risk sites were those on the central east coast, with July to January identified as the most at-risk months. Relatively high uptake rates were observed (exponential rate of 2% per day), similar to filter-feeding mussels, and meant that lobster accumulated toxins quickly. Similarly, lobsters were relatively fast detoxifiers, losing up to 3% PST per day, following bloom demise. Mussel sentinel lines were effective in indicating a risk of elevated PST in lobster hepatopancreas, with annual baseline monitoring costing approximately 0.06% of the industry value. In addition, it was determined that if the mean hepatopancreas PST levels in five individual lobsters from a site were <0.22 mg STX equiv. kg⁻¹, there is a 97.5% probability that any lobster from that site would be below the bivalve maximum level of 0.8 mg STX equiv. kg⁻¹. The combination of using a sentinel species to identify risk areas and sampling five individual lobsters at a particular site, provides a cost-effective strategy for managing PST risk in the Tasmanian commercial lobster fishery.     

Atmospheric and soil drought reduce nocturnal conductance in live oaks

Nocturnal and daytime whole-canopy transpiration rate (E) and conductance (g = E/VPD, where VPD is leaf to air vapor pressure difference) were assessed gravimetrically in drought-treated and well-watered 3-year-old saplings of live oak species (Quercus series Virentes Nixon) from the southeastern USA (Quercus virginiana Mill.) and Central America (Q. oleoides Cham. and Schlecter). Our objectives were to: (1) quantify nocturnal and daytime E and g in a controlled environment; (2) determine the impact of severe drought on nocturnal E and g; and (3) examine whether unavoidable water loss through the epidermis could account for nocturnal water loss. We calculated daytime E during peak daylight hours (between 0930 and 1330 h) and nocturnal E during complete darkness (between 2200 and 0500 h). In addition to reducing E and g during the daytime, drought-treated plants reduced nocturnal E and g on a whole-canopy basis by 62-64% and 59-61%, respectively, and on a leaf-level basis by 27-28% and 19-26%, respectively. In well-watered plants, nocturnal g declined with increasing VPD, providing evidence for stomatal regulation of nocturnal transpiration. In drought-treated plants, g was low and there was no relationship between nocturnal g and VPD, indicating that water loss could not be reduced further through stomatal regulation. Both daytime and nocturnal g declined curvilinearly with predawn water potential for all plants, but nocturnal g was unrelated to predawn water potentials below -1 MPa. The reductions in daytime and nocturnal E and g during drought were associated with decreases in whole-plant and leaf hydraulic conductances. Observed nocturnal g was within the same range as epidermal conductance for oak species determined in previous studies under a range of conditions. Nocturnal E rose from 6-8% of daytime E for well watered plants to 19-20% of daytime E for drought-treated plants. These results indicate that, during drought, saplings of live oak species reduce g to a minimum through stomatal closure, and experience unavoidable water loss through the epidermis.     

A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at‐risk pug dogs

BackgroundNecrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested.Hypothesis/ObjectivePug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME.AnimalsThirty‐six pug dogs less than 4 years of age asymptomatic for NME.MethodsProspective observational cohort study with germline genome‐wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination.ResultsThe overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at‐risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03).Conclusions and Clinical ImportanceOur findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at‐risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.     

Visuospatial skills are better predictors than dexterity for basic ultrasonographic and fluoroscopic skills in veterinary students

Radiological skills including ultrasonography and fluoroscopy, require a combination of manual dexterity and visuospatial skill to develop competency. The ability to detect veterinary students with an interest in radiology but who are deficient in these skills, may permit more individual adaptations to training programs, allowing for students training in radiology to achieve maximal potential. The objective of this cohort study was to investigate whether innate dexterity and visuospatial skill could be used to predict performance of basic ultrasound and fluoroscopic skills in veterinary students. Fifty veterinary students from the Ontario Veterinary College completed three tests of visuospatial ability, two tests of manual dexterity, a three‐dimensional mouse task, an ultrasound skill‐testing task, and a fluoroscopic skill‐testing task. Students who reported chopstick use completed the non‐dominant hand ultrasound task significantly faster than students who did not (P = 0.001). There was a significant positive association between scores on the Mental Rotations Test and time to complete the non‐dominant hand ultrasound task (P = 0.011) and fluoroscopy task (P = 0.029). No variables were associated with time to complete the dominant hand ultrasound task. The results of this study suggest that visuospatial skill, as assessed by the Mental Rotations Test, is a better predictor of baseline ultrasound and endovascular fluoroscopy skill than dexterity, with the exception of reported chopstick use, in veterinary students. Visuospatial skills can be developed and may be useful to include in the veterinary curriculum for students that are deficient, or students entering a field such as diagnostic imaging.