Analysis of the Ca2+ response of mycelial fungi to external effects by the recombinant aequorin method

Using the mutant strain Aspergillus awamori 66A producing a recombinant Ca2+-dependent photosensitive protein aequorin, the dynamics of Ca2+ was studied for the first time in the cytosol of the micromycetes exposed to stressful factors, such as an increase in extracellular Ca2+ to 50 mM, hypoosmotic shock, and mechanical shock. Cell response to stress proved to involve an increase in the Ca2+ concentration in the cytosol, which was determined from the amplitude of aequorin luminescence and the time of the amplitude enhancement and relaxation. The level of Ca 2+ response depended on the physiological stimulus. Inhibitory analysis with various agents that block Ca2+ channels and with agonists that specifically enhance the activity of the channels suggested that (1) the level of Ca2+ in the cytosol of micromycetes increases in response to stress because of the ion influx from both the growth medium and intracellular reservoirs and (2) the potential-dependent transport systems play the major role in the Ca2+ influx into the cytosol of the micromycete cells

Analysis of the Ca2+ response of mycelial fungi to external effects by the recombinant aequorin method

Using the mutant strain Aspergillus awamori 66A, producing the recombinant Ca2+ -dependent photosensitive protein aequorin, the dynamics of Ca2+ was studied for the first time in the cytosol of micromycetes exposed to stressful factors, such as an increase in extracellular Ca 2+ to 50 mM, hypoosmotic shock, and mechanical shock. The cell response to stress proved to involve an increase in the Ca2+ concentration in the cytosol, which was determined from the amplitude of aequorin luminescence and the time of the amplitude enhancement and relaxation. The level of the Ca2+ response depended on the physiological stimulus. Inhibitory analysis with various agents that block Ca2+ channels and with agonists that specifically enhance the activity of the channels suggested that (1) the level of Ca2+ in the cytosol of micromycetes increases in response to stress because of the ion influx from both the growth medium and intracellular reservoirs and (2) potential-dependent transport systems play the major role in the Ca2+ influx into the cytosol of the micromycete cells. © 2004 MAIK "Nauka/ Interperiodica"

DUNDRUM-2: Prospective validation of a structured professional judgment instrument assessing priority for admission from the waiting list for a forensic mental health hospital

<p>Abstract</p> <p>Background</p> <p>The criteria for deciding who should be admitted first from a waiting list to a forensic secure hospital are not necessarily the same as those for assessing need. Criteria were drafted qualitatively and tested in a prospective 'real life' observational study over a 6-month period.</p> <p>Methods</p> <p>A researcher rated all those presented at the weekly referrals meeting using the DUNDRUM-1 triage security scale and the DUNDRUM-2 triage urgency scale. The key outcome measure was whether or not the individual was admitted.</p> <p>Results</p> <p>Inter-rater reliability and internal consistency for the DUNDRUM-2 were acceptable. The DUNDRUM-1 triage security score and the DUNDRUM-2 triage urgency score correlated r = 0.663. At the time of admission, after a mean of 23.9 (SD35.9) days on the waiting list, those admitted had higher scores on the DUNDRUM-2 triage urgency scale than those not admitted, with no significant difference between locations (remand or sentenced prisoners, less secure hospitals) at the time of admission. Those admitted also had higher DUNDRUM-1 triage security scores. At baseline the receiver operating characteristic area under the curve for a combined score was the best predictor of admission while at the time of admission the DUNDRUM-2 triage urgency score had the largest AUC (0.912, 95% CI 0.838 to 0.986).</p> <p>Conclusions</p> <p>The triage urgency items and scale add predictive power to the decision to admit. This is particularly true in maintaining equitability between those referred from different locations.</p

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Priority setting for the implementation of artemisinin-based combination therapy policy in Tanzania: evaluation against the accountability for reasonableness framework

\ud Priority setting for artemisinin-based antimalarial drugs has become an integral part of malaria treatment policy change in malaria-endemic countries. Although these drugs are more efficacious, they are also more costly than the failing drugs. When Tanzania changed its National Malaria Treatment Policy in 2006, priority setting was an inevitable challenge. Artemether-lumefantrine was prioritised as the first-line drug for the management of uncomplicated malaria to be available at a subsidized price at public and faith-based healthcare facilities. This paper describes the priority-setting process, which involved the selection of a new first-line antimalarial drug in the implementation of artemisinin-based combination therapy policy. These descriptions were further evaluated against the four conditions of the accountability for easonableness framework. According to this framework, fair decisions must satisfy a set of publicity, relevance, appeals, and revision and enforcement conditions.In-depth interviews were held with key informants using pretested interview guides, supplemented with a review of the treatment guideline. Purposeful sampling was used in order to explore the perceptions of people with different backgrounds and perspectives. The analysis followed an editing organising style. Publicity: The selection decision of artemether-lumefantrine but not the rationale behind it was publicised through radio, television, and newspaper channels in the national language, Swahili. Relevance: The decision was grounded on evidences of clinical efficacy, safety, affordability, and formulation profile. Stakeholders were not adequately involved. There was neither an appeals mechanism to challenge the decision nor enforcement mechanisms to guarantee fairness of the decision outcomes. The priority-setting decision to use artemether-lumefantrine as the first-line antimalarial drug failed to satisfy the four conditions of the accountability for reasonableness framework. In our understanding, this is the first study to evaluate priority-setting decisions for new drugs in Tanzania against the accountability for reasonableness framework. In addition to the demand for enhanced stakeholder involvement, publicity, and transparency, the study also calls for the institution of formal appeals, revision, and regulatory mechanisms in the future change of malaria treatment policies.\u

Research led by participants: a new social contract for a new kind of research

In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish

Research led by participants: a new social contract for a new kind of research

In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish

Anti-Equivalence: Pragmatics of post-liberal dispute

In the early 21st century, liberal democracies have witnessed their foundational norms of critique and deliberation being disrupted by a combination of populist and technological forces. A distinctive style of dispute has appeared, in which a speaker denounces the unfairness of all liberal and institutional systems of equivalence, including the measures of law, economics and the various other ‘tests’ which convention scholars have deemed core to organisations. The article reviews how sociologists of critique have tended to treat critical capacities as oriented towards consensus, but then considers how technologies of real-time ‘control’ circumvent liberal critique altogether. In response, a different type of dispute emerges in the digital public sphere, which abandons equivalences in general, instead adopting a non-representational template of warfare. This style of post-liberal dispute is manifest in the rhetoric of populists, but does not originate there