Fungal stress biology: A preface to the Fungal Stress Responses special edition

There is currently an urgent need to increase global food security, reverse the trends of increasing cancer rates, protect environmental health, and mitigate climate change. Toward these ends, it is imperative to improve soil health and crop productivity, reduce food spoilage, reduce pesticide usage by increasing the use of biological control, optimize bioremediation of polluted sites, and generate energy from sustainable sources such as biofuels. This review focuses on fungi that can help provide solutions to such problems. We discuss key aspects of fungal stress biology in the context of the papers published in this Special Issue of Current Genetics. This area of biology has relevance to pure and applied research on fungal (and indeed other) systems, including biological control of insect pests, roles of saprotrophic fungi in agriculture and forestry, mycotoxin contamination of the food-supply chain, optimization of microbial fermentations including those used for bioethanol production, plant pathology, the limits of life on Earth, and astrobiology.

Development and Application of Medication Appropriateness Indicators for Persons with Advanced Dementia: A Feasibility Study

Background: No studies have been conducted in the UK context to date that categorise medications in terms of appropriateness for patients with advanced dementia, or that examine medication use in these vulnerable patients.

Objectives: The objectives of this study were to categorise the appropriateness of a comprehensive list of medications and medication classes for use in patients with advanced dementia; examine the feasibility of conducting a longitudinal prospective cohort study to collect clinical and medication use data; and determine the appropriateness of prescribing for nursing home residents with advanced dementia in Northern Ireland (NI), using the categories developed.

Methods: A three-round Delphi consensus panel survey of expert clinicians was used to categorise the appropriateness of medications for patients with advanced dementia [defined as having Functional Assessment Staging (FAST) scores ranging from 6E to 7F]. This was followed by a longitudinal prospective cohort feasibility study that was conducted in three nursing homes in NI. Clinical and medication use for participating residents with advanced dementia (FAST scores ranging from 6E to 7F) were collected and a short test of dementia severity administered. These data were collected at baseline and every 3 months for up to 9 months or until death. For those residents who died during the study period, data were also collected within 14 days of death. The appropriateness ratings from the consensus panel survey were retrospectively applied to residents’ medication data at each data collection timepoint to determine the appropriateness of medications prescribed for these residents.

Results: Consensus was achieved for 87 (90 %) of the 97 medications and medication classes included in the survey. Fifteen residents were recruited to participate in the longitudinal prospective cohort feasibility study, four of whom died during the data collection period. Mean numbers of medications prescribed per resident were 16.2 at baseline, 19.6 at 3 months, 17.4 at 6 months and 16.1 at 9 months. Fourteen residents at baseline were taking at least one medication considered by the consensus panel to be never appropriate, and approximately 25 % of medications prescribed were considered to be never appropriate. Post-death data collection indicated a decrease in the proportion of never appropriate medications and an increase in the proportion of always appropriate medications for those residents who died.

Conclusions: This study is the first to develop and apply medication appropriateness indicators for patients with advanced dementia in the UK setting. The Delphi consensus panel survey of expert clinicians was a suitable method of developing such indicators. It is feasible to collect information on quality of life, functional performance, physical comfort, neuropsychiatric symptoms and cognitive function for this subpopulation of nursing home residents with advanced dementia.

RNA interference in adult Ascaris suum - an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite

The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance.

Parasite neuropeptide biology:Seeding rational drug target selection?

The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Studies on hemopoietic chimerism following allogeneic bone marrow transplantation in the molecular biology era

Donor hematopoiesis or donor chimerism in the host following allogeneic bone marrow transplantation (BMT) has appeared crucial to the engraftment process. However, as molecular techniques exploiting neutral variation in human genetic material have been used in the study of chimerism, the detection of residual host cells or mixed hemopoietic chimerism has indicated that donor chimerism is not obligatory following BMT. This review focuses on the detection and significance of mixed chimerism (MC) in patients transplanted for both malignant and non-malignant hemopoietic disease and attempts to tease out the contribution of MC to engraftment, leukemia relapse, graft rejection and long-term disease-free survival.

Assessment of Anaerobic Biodegradation of Aromatic Hydrocarbons: The Impact of Molecular Biology Approaches

One of the most cost effective methods of pollution remediation is through natural attenuation where the resident microorganisms are responsible for the breakdown of pollutants (Dou et al. 2008). Other forms of bioremediation - such as analogue enrichment, composting and bio-venting - also use the microbes already present in a contaminated site to enhance the remediation process. In order for these approaches to be successful, in an industrial setting, some form of monitoring needs to take place enabling conclusions to be drawn about the degradation processes occurring. In this review we look at some key molecular biology techniques that have the potential to act as a monitoring tool for industries dealing with contaminated land. 

Report from the 2nd Summer School in Computational Biology organized by the Queen's University of Belfast

In this paper, we present a meeting report for the 2nd Summer School in Computational Biology organized by the Queen's University of Belfast. We describe the organization of the summer school, its underlying concept and student feedback we received after the completion of the summer school.

Glacial cirques as palaeoenvironmental indicators: their potential and limitations

Glacial cirques are armchair-shaped erosional hollows, typified by steep headwalls and, often, overdeepened floors. They reflect former regions of glacier initiation, and their distribution is, therefore, linked to palaeoclimate. Because of this association, cirques can be analysed for the information they provide about past environments, an approach that has a strong heritage, and has seen resurgence over recent years. This paper provides a critical assessment of what cirques can tell us about past environments, and considers their reliability as palaeoenvironmental proxies. Specific focus is placed on information that can be obtained from consideration of cirque distribution, aspect, altitude, and morphometry. The paper highlights the fact that cirques potentially provide information about the style, duration and intensity of former glaciation, as well as information about past temperatures, precipitation gradients, cloud-cover and wind directions. In all, cirques are considered a valuable source of palaeoenvironmental information (if used judiciously), particularly as they are ubiquitous within formerly glaciated mountain ranges globally, thus making regional or even global scale studies possible. Furthermore, cirques often occupy remote and inaccessible regions where other palaeoenvironmental proxies may be limited or lacking.