Purification of a chymotrypsin-like enzyme present on adult Schistosoma mansoni worms from infected mice and its characterization as a host carboxylesterase

A serine protease-like enzyme found in detergent extracts of Schistosoma mansoni adult worms perfused from infected mice has been purified from mouse blood and further characterized. The enzyme is approximately 85 kDa and hydrolyses N-acetyl-DL-phenylalanine β-naphthyl–ester, a chromogenic substrate for chymotrypsin-like enzymes. The enzyme from S. mansoni worms appears to be antigenically and enzymatically similar to a molecule that is present in normal mouse blood and so is seemingly host-derived. The enzyme was partially purified by depleting normal mouse serum of albumin using sodium chloride and cold ethanol, followed by repeated rounds of purification by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified material was subjected to tandem mass spectrometry and its derived peptides found to belong to mouse carboxylesterase 1C. Its ability to hydrolyse α- or β-naphthyl acetates, which are general esterase substrates, has been confirmed. A similar carboxylesterase was purified and characterized from rat blood. Additional evidence to support identification of the enzyme as a carboxylesterase has been provided. Possible roles of the enzyme in the mouse host–parasite relationship could be to ease the passage of worms through the host's blood vessels and/or in immune evasion

Climate Change Affects Reproductive Phenology in Lianas of Australia’s Wet Tropics

Lianas are increasing in abundance in many tropical forests. This increase can alter forest structure and decrease both carbon storage and tree diversity via antagonistic relationships between lianas and their host trees. Climate change is postulated as an underlying driver of increasing liana abundances, via increases in dry-season length, forest-disturbance events, and atmospheric CO2 concentrations; all factors thought to favour lianas. However, the impact of climate change on liana reproductive phenology, an underlying determinant of liana abundance, has been little studied, particularly outside of Neotropical forests. Over a 15-year period (2000–2014), we examined the phenological patterns of a liana community in intact rainforests of the Wet Tropics bioregion of Australia; a World Heritage Area and hotspot of floral diversity. Specifically, we assessed (1) flowering and fruiting patterns of liana species; (2) potential climate drivers of flowering and fruiting activity; and (3) the influence of El Niño-related climatic disturbances on liana phenology. We found that flowering and fruiting of the studied liana species increased over time. Liana reproduction, moreover, rose in apparent response to higher temperatures and reduced rainfall. Finally, we found flowering and fruiting of the liana species increased following El Niño events. These results suggest that liana reproduction and abundance are likely to increase under predicted future climate regimes, with potentially important impacts on the survival, growth, and reproduction of resident trees and thus the overall health of Australian tropical rainforests

Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans

AbstractA reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 ± 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin.In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by ≥ 10 ejection fraction units to <55% the isovolumetric relaxation time was prolonged (from 66 ± 18 to 84 ± 24 ms, p < 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction.A >37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose.In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment

Towards a Parasitic Ethics

The parasite is widely conceived as a negative figure that takes without giving; perceived as an agent of corruption and destruction, it is subjected to programmes of eradication and expulsion across cultural, economic, political and ethical contexts. This paper offers an alternative approach to the status of parasitic relations in light of Michel Serres’s The Parasite, elaborated through ethnographic research into the after-hours culture and hidden economy of London’s Borough Market. We highlight the mutual dependence of agents in host-parasite networks according to what we term ‘general parasitism’, while inquiring into its ethical potential. Ultimately, we argue that while taking into account the near ubiquity of parasitic relations cannot form the basis for any concrete axiomatic ethical paradigm, it should at least encourage an ethics of hesitation before judgement when faced with any apparent instance of parasitism: to presume that parasitism is undesirable and unethical is itself undesirable and unethical

Assessing the effects of a drought experiment on the reproductive phenology and ecophysiology of a wet tropical rainforest community

Climate change is expected to increase the intensity and occurrence of drought in tropical regions, potentially affecting the phenology and physiology of tree species. Phenological activity may respond to a drying and warming environment by advancing reproductive timing, and/or diminishing the production of flowers and fruits. These changes have the potential to disrupt important ecological processes, with potentially wide-ranging effects on tropical forest function. Here, we analysed the monthly flowering and fruiting phenology of a tree community (337 individuals from 30 species) over seven years in a lowland tropical rainforest in north-eastern Australia, and its response to a through fall exclusion drought experiment (TFE) that was carried out from 2016 to 2018 (three years), excluding approximately 30% of rainfall. We further examined the eco-physiological effects of the TFE on the elemental (C:N) and stable isotope (d13C and d15N) composition of leaves, and on the stable isotope composition (d13C and d18O) of stem wood of four tree species. At the community level, there was no detectable effect of the TFE on flowering activity overall but there was a significant effect recorded on fruiting and varying responses from the selected species. The reproductive phenology and physiology of the four species examined in detail were largely resistant to impacts of the TFE treatment. One canopy species in the TFE significantly increased in fruiting and flowering activity whereas one understory species decreased significantly in both. There was a significant interaction between the TFE treatment and season on leaf C:N for two species. Stable isotope responses were also variable among species, indicating species-specific responses to the TFE. Thus, we did not observe consistent patterns in physiological and phenological changes in the tree community within the three years of TFE treatment examined in this study

A new P-wave tomographic model (cap22) for North America: implications for the subduction and cratonic metasomatic modification history of western Canada and Alaska

Our understanding of the present-day state and evolution of the Canadian and Alaskan mantle is hindered by a lack of absolute P-wavespeed constraints that provide complementary sensitivity to composition in conjunction with existing S-wavespeed models. Consequently, cratonic modification, orogenic history of western North America and complexities within the Alaskan Proto-Pacific subduction system remain enigmatic. One challenge concerns the difficulties in extracting absolute arrival-time measurements from often-noisy data recorded by temporary seismograph networks required to fill gaps in continental and global databases. Using the Absolute Arrival-time Recovery Method (AARM), we extract >180,000 new absolute arrival-time residuals from seismograph stations across Canada and Alaska and combine these data with USArray and global arrival-time data from the contiguous US and Alaska. We develop a new absolute P-wavespeed tomographic model, CAP22, spanning North America that significantly improves resolution in Canada and Alaska over previous models. Slow wavespeeds below the Canadian Cordillera sharply abut fast wavespeeds of the continental interior at the Rocky Mountain Trench in southwest Canada. Slow wavespeeds below the Mackenzie Mountains continue farther inland in northwest Canada, indicating Proterozoic-Archean metasomatism of the Slave craton. Inherited tectonic lineaments colocated with this north-south wavespeed boundary suggest that both the crust and mantle may control Cordilleran orogenic processes. In Alaska, fast upper mantle wavespeeds below the Wrangell Volcanic Field favor a conventional subduction related mechanism for volcanism. Finally, seismic evidence for the subducted Kula and Yukon slabs indicate tectonic reconstructions of western North America may require revision

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Should applicants to Nottingham University Medical School study a non-science A-level? A cohort study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that studying non-science subjects at A-level should be compulsory for medical students. Our admissions criteria specify only Biology, Chemistry and one or more additional subjects. This study aimed to determine whether studying a non-science subject for A-level is an independent predictor of achievement on the undergraduate medical course.</p> <p>Methods</p> <p>The subjects of this retrospective cohort study were 164 students from one entry-year group (October 2000), who progressed normally on the 5-year undergraduate medical course at Nottingham. Pre-admission academic and socio-demographic data and undergraduate course marks were obtained. T-test and hierarchical multiple linear regression analyses were undertaken to identify independent predictors of five course outcomes at different stages throughout the course.</p> <p>Results</p> <p>There was no evidence that the choice of science or non-science as the third or fourth A-level subject had any influence on course performance. Demographic variables (age group, sex, and fee status) had some predictive value but ethnicity did not. Pre-clinical course performance was the strongest predictor in the clinical phases (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and pre-clinical Themes C&D (skills) predicted Clinical Skills, p = < 0.01).</p> <p>Conclusion</p> <p>This study of one year group at Nottingham Medical School provided no evidence that the admissions policy on A-level requirements should specify the choice of third or fourth subject.</p

‘No Time to be Lost!’: Ethical Considerations on Consent for Inclusion in Emergency Pharmacological Research in Severe Traumatic Brain Injury in the European Union

Severe Traumatic Brain Injury (TBI) remains a major cause of death and disability afflicting mostly young adult males and elderly people, resulting in high economic costs to society. Therapeutic approaches focus on reducing the risk on secondary brain injury. Specific ethical issues pertaining in clinical testing of pharmacological neuroprotective agents in TBI include the emergency nature of the research, the incapacity of the patients to informed consent before inclusion, short therapeutic time windows, and a risk-benefit ratio based on concept that in relation to the severity of the trauma, significant adverse side effects may be acceptable for possible beneficial treatments. Randomized controlled phase III trials investigating the safety and efficacy of agents in TBI with promising benefit, conducted in acute emergency situations with short therapeutic time windows, should allow randomization under deferred consent or waiver of consent. Making progress in knowledge of treatment in acute neurological and other intensive care conditions is only possible if national regulations and legislations allow waiver of consent or deferred consent for clinical trials