The fungus that came in from the cold: dry rot's pre-adapted ability to invade buildings.

Many organisms benefit from being pre-adapted to niches shaped by human activity, and have successfully invaded man-made habitats. One such species is the dry rot fungus Serpula lacrymans, which has a wide distribution in buildings in temperate and boreal regions, where it decomposes coniferous construction wood. Comparative genomic analyses and growth experiments using this species and its wild relatives revealed that S. lacrymans evolved a very effective brown rot decay compared to its wild relatives, enabling an extremely rapid decay in buildings under suitable conditions. Adaptations in intracellular transport machineries promoting hyphal growth, and nutrient and water transport may explain why it is has become a successful invader of timber in houses. Further, we demonstrate that S. lacrymans has poor combative ability in our experimental setup, compared to other brown rot fungi. In sheltered indoor conditions, the dry rot fungus may have limited encounters with other wood decay fungi compared to its wild relatives. Overall, our analyses indicate that the dry rot fungus is an ecological specialist with poor combative ability against other fungi.

Presence and extent of cardiac computed tomography angiography defined coronary artery disease in patients presenting with syncope.

BACKGROUND: In syncope patients, presence of coronary artery disease (CAD) is associated with poor prognosis. However, data concerning CAD prevalence in syncope patients without known cardiovascular disease are lacking. Therefore, the aim of this study was to investigate presence and extent of CAD in syncope patients. METHODS: We included 142 consecutive patients presenting with syncope at the outpatient cardiology clinic who underwent coronary computed tomography (CT) angiography. Syncope type was ascertained by two reviewers, blinded for coronary CT angiography results. Of the patients, 49 had cardiac syncope (arrhythmia or structural cardiopulmonary disease) and 93 had non-cardiac syncope (reflex [neurally-mediated], orthostatic or of unknown cause). Cardiac syncope patients were compared with matched stable chest pain patients regarding age, gender, smoking status, diabetes mellitus type 2 and systolic blood pressure. RESULTS: Distribution of CAD presence and extent in cardiac and non-cardiac syncope patients was as follows: 72% versus 48% any CAD; 31% versus 26% mild, 8% versus 14% moderate and 33% versus 7% severe CAD. Compared with non-cardiac syncope, patients with cardiac syncope had a significantly higher CAD presence and extent (p = 0.001). Coronary calcium score, segment involvement and stenosis score were also higher in cardiac syncope patients (p-values ≤0.004). Compared to the chest pain control group, patients with cardiac syncope showed a higher, however, non-significant, prevalence of any CAD (72% versus 63%) and severe CAD (33% versus 19%). CONCLUSION: Patients with cardiac syncope show a high presence and extent of CAD in contrast to non-cardiac syncope patients. These results suggest that CAD may play an important role in the occurrence of cardiac syncope.

Oxygen-iron interaction in liquid lead-bismuth eutectic alloy.

Iron released by steel corrosion was found to be a key impurity in reactions with dissolved oxygen in liquid lead-bismuth eutectic alloys. The iron-oxygen-magnetite equilibrium was characterized, allowing the quantification of phenomena that are important for long-term operation of lead-alloy based installations such as corrosion rate control and management of precipitates.

Joint research towards a better radiation protection-highlights of the Fifth MELODI Workshop.

MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.

Electrophysiological registration of phonological perception in the subthalamic nucleus of patients with Parkinson's Disease.

Phonological processing is usually associated with the activation of cortical areas, especially in the left cerebral hemisphere. This study examined if phonologically elicited evoked potentials can be recorded directly from the subthalamic nucleus in patients with Parkinson's Disease (PD). Seven PD patients who had undergone implantation of deep brain electrodes for the stimulation of the subthalamic nucleus were included. Local field potentials were recorded in a pre-attentive auditory phonological task, an attentive auditory phonological discrimination task, and a word recognition task. Auditory evoked potentials related to phonological, but not lexical processing, could be demonstrated in the subthalamic nucleus for all three tasks. Only minor changes were found after levodopa administration. This study demonstrates that the subthalamic nucleus is involved in early phonological perception, which puts the subthalamic nucleus in a position to modify phonological perception in a larger cortico-subcortical network.

Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy.

Many tumors express one or more proteins that are either absent or hardly present in normal tissues, and which can be targeted by radiopharmaceuticals for either visualization of tumor cells or for targeted therapy. Radiopharmaceuticals can consist of a radionuclide and a carrier molecule that interacts with the tumor target and as such guides the attached radionuclide to the right spot. Radiopharmaceuticals hold great promise for the future of oncology by providing early, precise diagnosis and better, personalized treatment. Most advanced developments with marketed products are based on whole antibodies or antibody fragments as carrier molecules. However, a substantial number of (pre)clinical studies indicate that radiopharmaceuticals based on other carrier molecules, such as peptides, nonimmunoglobulin scaffolds, or nucleic acids may be valuable alternatives. In this review, we discuss the biological molecules that can deliver radionuclide payloads to tumor cells in terms of their structure, the selection procedure, their (pre)clinical status, and advantages or obstacles to their use in a radiopharmaceutical design. We also consider the plethora of molecular targets existing on cancer cells that can be targeted by radiopharmaceuticals, as well as how to select a radionuclide for a given diagnostic or therapeutic product.

Antihypertensive effectiveness of aliskiren for the 'real-world' management of hypertension: multilevel modelling of 180-day blood pressure outcomes (the Belgian DRIVER Study).

AIMS: The 'DRIVER' study was designed to investigate the 'real-world' effectiveness of aliskiren-based treatment of hypertension. This article reports the 180-day blood pressure (BP) outcomes, and the multilevel (physician- and patient-level) determinants thereof. METHODS AND RESULTS: DRIVER was a prospective, observational, open-label, multi-centre, pharmaco-epidemiologic study of hypertensive patients treated with aliskiren in whom prior treatment failed or was not tolerated. 2070 patients (enrolled by 426 physicians) were enrolled; 1695 patients (81.9%) completed the 180-day aliskiren treatment period. Mean patient age was 64.2 ± 12.1 years; 53.7% were men, 25.3% diabetic and 40.7% had a high or very high cardiovascular (CV) risk. At 180 days, the mean ± SD reductions in systolic and diastolic BP were -22.9 ± 16.7 mmHg and -10.5 ± 10.9 mmHg respectively (both p < .001). 2007 and 2009 guideline-defined BP control was achieved in 36.4% and 56.3% of patients, respectively (both p < .001). 64.2% of eligible patients had a reduction in CV risk (p < .001). A physician-level class effect was responsible for 22.8% and 28.1% of variability in systolic and diastolic BP, respectively, for 20.1% of variability in BP control, and for 16.1% of variability in the reduction of CV risk. Both patient- (e.g. adherence) and physician-related factors (e.g. age and knowledge) were significant in profiling best response to treatment with aliskiren. Adverse events reported in this article were consistent with the aliskiren scientific leaflet. CONCLUSION: Aliskiren is safe and effective in reducing BP, improving BP control and reducing global CV risk in a 'real-world' setting and for patients in whom prior treatment failed or was not tolerated. Optimising treatment adherence and strategic medical education may be ways of improving BP outcomes in patients with hypertension.

Characterization of nanoparticles in diluted clear solutions for Silicalite-1 zeolite synthesis using liquid 29Si NMR, SAXS and DLS.

Clear solutions for colloidal Silicalite-1 synthesis were prepared by reacting tetraethylorthosilicate in aqueous tetrapropylammonium hydroxide solution. A dilution series with water resulting in clear solutions with a TEOS ratio TPAOH ratio H2O molar ratio of 25 : 9 : 152 up to 25 : 9 : 15,000 was analysed using liquid 29Si nuclear magnetic resonance (NMR), synchrotron small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Particle sizes were derived independently from DLS and from the combination of SAXS and NMR. NMR allowed quantitative characterization of silicon distributed over nanoparticles and dissolved oligomeric silicate polyanions. In all samples studied, the majority of silicon (78-90%) was incorporated in the nanoparticle fraction. In concentrated suspensions, silicate oligomers were mostly double-ring species (D3R, D4R, D5R, D6R). Dilution with water caused their depolymerisation. Contrarily, the internal condensation and size of nanoparticles increased with increasing dilution. SAXS revealed a decrease of effective nanoparticle surface charge upon dilution, reducing the effective particle interactions. With DLS, the reduction of nanoparticle interactions could be confirmed monitoring the collective diffusion mode. The observed evolution of nanoparticle characteristics provides insight in the acceleration of the Silicalite-1 crystallization upon dilution, in view of different crystallization models proposed in the literature.

Ydc1p ceramidase triggers organelle fragmentation, apoptosis and accelerated ageing in yeast.

Saccharomyces cerevisiae dihydroceramidase Ydc1p hydrolyzes ceramide, resulting in accumulation of free long-chain bases and their phosphates. Yeast mutants lacking YDC1 are characterized by increased chronological lifespan. Moreover, we found YDC1 up-regulated in a yeast mutant displaying reduced chronological lifespan. These data suggest an important role for Ydc1p in chronological lifespan determination in yeast. Mitochondria are known to play an important role in chronological lifespan and apoptosis. In this study we demonstrated that overexpression of YDC1 results in reduced chronological lifespan and increased apoptotic cell death. We found YDC1 overexpression to result in mitochondrial fragmentation and dysfunction. Interestingly, vacuoles also appeared to be fragmented and dysfunctional upon YDC1 overexpressing. Exogenous addition of ceramide to YDC1-overexpressing cultures increased chronological lifespan and restored organelle function. In conclusion, this study describes a direct link between ceramide metabolism in yeast and mitochondrial and vacuolar fragmentation and function, with consequences for chronological lifespan in yeast.

The mode of antifungal action of plant, insect and human defensins.

Defensins are small (~5 kDa), basic, cysteine-rich antimicrobial peptides that fulfill an important role in the innate immunity of their host by combating pathogenic invading micro-organisms. Defensins can inhibit the growth or virulence of microorganisms directly or can do so indirectly by enhancing the host's immune system. Because of their wide distribution in nature, defensins are believed to be ancient molecules with a common ancestor that arose more than a billion years ago. This review summarizes current knowledge concerning the mode of antifungal action of plant, insect and human defensins.

The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis.

Mycorrhizal symbioses--the union of roots and soil fungi--are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants. Boreal, temperate and montane forests all depend on ectomycorrhizae. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome assembly contains approximately 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector-type small secreted proteins (SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and nitrogen cycles that are fundamental to sustainable plant productivity.

Tuberculosis and tuberculosis control in European prisons.

OBJECTIVE: Correctional facilities have often been cited as reservoirs for tuberculosis (TB), presenting a potential threat to the general population. Although correctional facilities are recognised as ideal settings for interventions, little is known about the TB epidemiology within them. The purpose of our survey was to collect data on TB in prisons of the WHO European Region and on existing control measures. DESIGN: A questionnaire was sent to 52 EuroTB correspondents asking for 2002 data on the total number of inmates, number of prisoners with TB, resistance rates, screening strategies, monitoring and responsibilities. RESULTS: Twenty-two (42.3%) countries completed the questionnaire. The median TB notification rate was 232 per 100,000 inmates (0-17,808). Prisoners had up to 83.6 times more TB than civilians. The majority (90.9%) of the participating countries reported performing active screening for TB on entry into prison, with a median detection rate of 393/100,000 (42-2362). Of the respondent countries, 81.8% claimed to perform contact investigations and 86.4% to house infectious TB patients separately. CONCLUSION: Although response to this survey was only 42.3% and might be biased by a country's engagement in TB control in prisons, the results highlight the vulnerability of prisoners to TB and emphasise the need for adequate case-finding and containment strategies in prison.

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Fungal sphingolipids as targets for the development of selective antifungal therapeutics.

Sphingolipids are essential membrane components, present in all eukaryotic cells, but structurally distinct in mammalian and fungal cells. Therefore, they represent an attractive new target for the development of novel antimycotics. This review will briefly highlight sphingolipid biosynthesis and functions in the yeast Saccharomyces cerevisiae. In addition, naturally occurring antifungal compounds that interact with fungal-specific sphingolipids, resulting in fungal growth arrest, will be discussed regarding their mode of action, and therapeutic value. These compounds include plant and insect defensins, syringomycin E and antifungal antibodies to sphingolipids.

Fast separations on monolithic silica columns: method transfer, robustness and column ageing for some case studies.

Six separation methods, developed on conventional silica high performance liquid chromatography (HPLC) columns were transferred to monolithic silica columns of 5 and 10 cm length. The transferred methods include the separation of an alkylbenzene mixture, the separations of drugs from their impurities (nimesulide, tetracycline, phenoxymethylpenicillin and erythromycin) and the separation of a green tea extract. The transfer of the first three methods was successful while for the latter three it was not. Increasing the flow rate up to 9 ml/min (where possible) inversely decreased the analysis time of the successfully transferred methods to 48 s (alkylbenzene mixture) 1.8 min (nimesulide mixture) and 3 min (tetracycline mixture) while still reasonable well separated peaks were obtained. The robustness and repeatability of the transferred and accelerated separations was found to be acceptable. Despite the use of flow rates up to 9 ml/min and frequent mobile phase changes with pH values varying from 3.5 to 7, the column performance was found to be rather constant and the column ageing to be minimal.

Chronic radiodermatitis following percutaneous coronary interventions: a report of two cases.

We describe two patients in whom chronic radiodermatitis with therapy-resistant ulceration of the right scapular region developed, following percutaneous coronary intervention with fluoroscopic imaging. Contrary to most reported cases in the literature, which involve numerous cardiac catheterization procedures, in both patients described here the total radiation dose was given during two successive procedures, involving difficult and prolonged coronary intervention with stent implantation. In both cases, local treatment of the ulcerative lesions was insufficient, necessitating excision of the radiodermatitis area and replacement with a skin graft, with good therapeutic result. The incidence of radiodermatitis after percutaneous coronary interventions is rising with the increasing number and complexity of these procedures. The main risk factor is a long duration of fluoroscopy using the same incidence. The skin lesions encompass a wide spectrum, ranging from erythema, telangiectasia, atrophy, hyperpigmentation and hypopigmentation to necrosis, chronic ulceration and squamous cell carcinoma. The lesions can appear from 15 days to 10 years after the procedure. To prevent radiation-induced injury, the radiation dose has to be limited and monitored. Also, careful inspection of the skin at the site of exposure is necessary and the radiographic beam has to be restricted to the smallest field size. A good clinical follow-up at regular intervals is important after long and complicated procedures.

Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.