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The mfl-riboswitch regulates expression of ribonucleotide reductase subunit in Mesoplasma florum by binding to 2´-deoxyguanosine and thereby promoting transcription termination. We characterized the structure of the ligand-bound aptamer domain by NMR spectroscopy and compared the mfl-aptamer to the aptamer domain of the closely related purine-sensing riboswitches. We show that the mfl-aptamer accommodates the extra 2´-deoxyribose unit of the ligand by forming a more relaxed binding pocket than these found in the purine-sensing riboswitches. Tertiary structures of the xpt-aptamer bound to guanine and of the mfl-aptamer bound to 2´-deoxyguanosine exhibit very similar features, although the sequence of the mfl-aptamer contains several alterations compared to the purine-aptamer consensus sequence. These alterations include the truncation of a hairpin loop which is crucial for complex formation in all purine-sensing riboswitches characterized to date. We further defined structural features and ligand binding requirements of the free mfl-aptamer and found that the presence of Mg2+ is not essential for complex formation, but facilitates ligand binding by promoting pre-organization of key structural motifs in the free aptamer.
RNA thermometers are translational control elements that regulate the expression of bacterial heat shock and virulence genes. They fold into complex secondary structures that block translation at low temperatures. A temperature increase releases the ribosome binding site and thus permits translation initiation. In fourU-type RNA thermometers, the AGGA sequence of the SD region is paired with four consecutive uridines. We investigated the melting points of the wild-type and mutant sequences. It was decreased by 5°C when a stabilizing GC basepair was exchanged by an AU pair or increased by 11°C when an internal AG mismatch was converted to a GC pair, respectively. Stabilized or destabilized RNA structures are directly correlated with decreased or increased in vivo gene expression, respectively. Mg2+ also affected the melting point of the fourU thermometer. Variations of the Mg2+ concentration in the physiological range between 1 and 2 mM translated into a 2.8°C shift of the melting point. Thus, Mg2+ binding to the hairpin RNA is regulatory relevant. Applying three different NMR techniques, two Mg2+ binding sites were found in the hairpin structure. One of these binding sites could be identified as outer sphere binding site that is located within the fourU motif. Binding of the two Mg2+ ions exhibits a positive cooperativity with a Hill coefficient of 1.47. Free energy values delta G for Mg2+ binding determined by NMR are in agreement with data determined from CD measurements. Physiological Mg2+ concentrations reduce enthalpy and entropy values of uncorrelated base pair opening processes for almost all nucleobases.
The plastids of cryptophytes, haptophytes, and heterokontophytes (stramenopiles) (together once known as chromists) are surrounded by four membranes, reflecting the origin of these plastids through secondary endosymbiosis. They share this trait with apicomplexans, which are alveolates, the plastids of which have been suggested to stem from the same secondary symbiotic event and therefore form a phylogenetic clade, the chromalveolates. The chromists are quantitatively the most important eukaryotic contributors to primary production in marine ecosystems. The mechanisms of protein import across their four plastid membranes are still poorly understood. Components of an endoplasmic reticulum-associated degradation (ERAD) machinery in cryptophytes, partially encoded by the reduced genome of the secondary symbiont (the nucleomorph), are implicated in protein transport across the second outermost plastid membrane. Here, we show that the haptophyte Emiliania huxleyi, like cryptophytes, stramenopiles, and apicomplexans, possesses a nuclear-encoded symbiont-specific ERAD machinery (SELMA, symbiont-specific ERAD-like machinery) in addition to the host ERAD system, with targeting signals that are able to direct green fluorescent protein or yellow fluorescent protein to the predicted cellular localization in transformed cells of the stramenopile Phaeodactylum tricornutum. Phylogenies of the duplicated ERAD factors reveal that all SELMA components trace back to a red algal origin. In contrast, the host copies of cryptophytes and haptophytes associate with the green lineage to the exclusion of stramenopiles and alveolates. Although all chromalveolates with four membrane-bound plastids possess the SELMA system, this has apparently not arisen in a single endosymbiotic event. Thus, our data do not support the chromalveolate hypothesis. Key words: Emiliania huxleyi, secondary endosymbiosis, chromalveolate, hypothesis, complex plastid, plastid protein import, algal evolution
Extending the carotenoid pathway to astaxanthin in plants is of scientific and industrial interest. However, expression of a microbial beta-carotene ketolase (BKT) that catalyses the formation of ketocarotenoids in transgenic plants typically results in low levels of astaxanthin. The low efficiency of BKTs in ketolating zeaxanthin to astaxanthin is proposed to be the major limitation for astaxanthin accumulation in engineered plants. To verify this hypothesis, several algal BKTs were functionally characterized using an Escherichia coli system and three BKTs were identified, with high (up to 85%), moderate (~38%), and low (~1%) conversion rate from zeaxanthin to astaxanthin from Chlamydomonas reinhardtii (CrBKT), Chlorella zofingiensis (CzBKT), and Haematococcus pluvialis (HpBKT3), respectively. Transgenic Arabidopsis thaliana expressing the CrBKT developed orange leaves which accumulated astaxanthin up to 2 mg g -1 dry weight with a 1.8-fold increase in total carotenoids. In contrast, the expression of CzBKT resulted in much lower astaxanthin content (0.24 mg g -1 dry weight), whereas HpBKT3 was unable to mediate synthesis of astaxanthin in A. thaliana. The none-native astaxanthin was found mostly in a free form integrated into the light-harvesting complexes of photosystem II in young leaves but in esterified forms in senescent leaves. The alteration of carotenoids did not affect chlorophyll content, plant growth, or development significantly. The astaxanthin-producing plants were more tolerant to high light as shown by reduced lipid peroxidation. This study advances a decisive step towards the utilization of plants for the production of high-value astaxanthin. Keywords: Arabidopsis thaliana, astaxanthin, beta-carotene ketolase, carotenoid, Haematococcus pluvialis
Background: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed ‘chronic cerebrospinal venous insufficiency’ (CCSVI) was proposed, provoking significant attention in the media and scientific community.
Methods: Twenty MS patients (mean age 42.2±13.3 years; median Extended Disability Status Scale 3.0, range 0–6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA≤0.3 cm2 indicated ‘stenosis,’ and IJV-VCSA decrease from supine to upright position ‘reverted postural control.’ The sonographer, data analyser and statistician were blinded to the patient/control status of the participants.
Results: No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA≤0.3 cm2 was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI.
Conclusions: This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.
The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery. Keywords: apoptosis; pancreatic cancer; TRAIL; IAPs; mitochondria
Novel insights into the synergistic interaction of Bortezomib and TRAIL: tBid provides the link
(2011)
The proteasome inhibitor Bortezomib has been identified as a potent enhancer of TRAIL-induced apoptosis in several human cancers. However, the identification of the underlying molecular mechanisms of this synergistic cell death induction has been ongoing over the last years. A recent study identifies a new mechanism of action for the synergism of TRAIL and Bortezomib.
Background: Working conditions of nursery school teachers have not been scrutinized thoroughly in scientific research. Only a few studies have so far examined work-load and strain in this profession. Preferably, subjective perceptions should be corroborated by data that can be quantified more objectively and accurately. The aim of the present observational field study was to evaluate pedagogical staffs' workflow.
Methods: In 2009 eleven educators in a day care centre were observed throughout three complete workdays. A total of 250 working hours were recorded.
Results: An educators' workday lasted on average 07:46:59 h (SD = 01:01:10 h).Within this time span, an average of 02:20:46 h (30.14%, SD = 00:28:07 h) were spent on caring, 01:44:18 h on playing (22.33%, SD = 00:54:12 h), 00:49:37 h on educational work (10.62%, SD = 00:40:09), and only 00:05:38 h on individual child contact (1.21%, SD = 00:04:58 h).
Conclusion: For the first time, educators' workflow in day care centres was studied in real time. Some of the educators' self-reported problems were corroborated. The results of this study form a basis upon which further investigations can be built and measures can be developed for an overall improvement of child care.
This article presents new directions of literary and media memory studies. It distinguishes between (1) the study of "traumatic pasts", i.e. representations of war and violence in literature and other media, (2) diachronic and intermedial approaches to "literary afterlives" and (3) recent insights into the inherent transculturality of memory and their consequences for literary and media studies. Keywords: cultural memory studies, literature and memory, media and memory, transcultural memory
Climate change research is increasingly focusing on the dynamics among species, ecosystems and climates. Better data about the historical behaviours of these dynamics are urgently needed. Such data are already available from ecology, archaeology, palaeontology and geology, but their integration into climate change research is hampered by differences in their temporal and geographical scales. One productive way to unite data across scales is the study of functional morphological traits, which can form a common denominator for studying interactions between species and climate across taxa, across ecosystems, across space and through time—an approach we call ‘ecometrics’. The sampling methods that have become established in palaeontology to standardize over different scales can be synthesized with tools from community ecology and climate change biology to improve our understanding of the dynamics among species, ecosystems, climates and earth systems over time. Developing these approaches into an integrative climate change biology will help enrich our understanding of the changes our modern world is undergoing.
The influence of dispersal limitation on species ranges remains controversial. Considering the dramatic impacts of the last glaciation in Europe, species might not have tracked climate changes through time and, as a consequence, their present-day ranges might be in disequilibrium with current climate. For 1016 European plant species, we assessed the relative importance of current climate and limited postglacial migration in determining species ranges using regression modelling and explanatory variables representing climate, and a novel species-specific hind-casting-based measure of accessibility to postglacial colonization. Climate was important for all species, while postglacial colonization also constrained the ranges of more than 50 per cent of the species. On average, climate explained five times more variation in species ranges than accessibility, but accessibility was the strongest determinant for one-sixth of the species. Accessibility was particularly important for species with limited long-distance dispersal ability, with southern glacial ranges, seed plants compared with ferns, and small-range species in southern Europe. In addition, accessibility explained one-third of the variation in species' disequilibrium with climate as measured by the realized/potential range size ratio computed with niche modelling. In conclusion, we show that although climate is the dominant broad-scale determinant of European plant species ranges, constrained dispersal plays an important supplementary role.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Background: The zinc finger transcription factor Egr-1 (Early growth response 1) is central to several growth factors and represents an important activator of target genes not only involved in physiological processes like embryogenesis and neonatal development, but also in a variety of pathophysiological processes, for example atherosclerosis or cancer. Current options to investigate its transcription and activation in vivo are end-point measurements that do not provide insights into dynamic changes in the living organism. Results: We developed a transgenic mouse (Egr-1-luc) in which the luciferase reporter gene is under the control of the murine Egr-1 promoter providing a versatile tool to study the time course of Egr-1 activation in vivo. In neonatal mice, bioluminescence imaging revealed a high Egr-1 promoter activity reaching basal levels three weeks after birth with activity at snout, ears and paws. Using a model of partial hepatectomy we could show that Egr-1 promoter activity and Egr-1 mRNA levels were increased in the regenerating liver. In a model of wound healing, we demonstrated that Egr-1 promoter activity was upregulated at the site of injury. Conclusion: Taken together, we have developed a transgenic mouse model that allows real time in vivo imaging of the Egr-1 promoter activity. The ability to monitor and quantify Egr-1 activity in the living organism may facilitate a better understanding of Egr-1 function in vivo. Additional File 1: BLI of adult Egr-1-luc mice with opened body cavity. Transgenic Egr-1-luc mice (one month old) received 6 mg luciferin in 100 μl PBS by intraperitoneal injection. Ten minutes thereafter the animal was killed by cervical dislocation, the body cavity opened immediately, skin from the ventral side partially removed and BLI measurement was carried out (10 min signal collection, setting 'high resolution'). A representative animal is shown with similar amplification setting as in Figure 2A.
Background: Factors and processes shaping the population structure and spatial distribution of genetic diversity across a species' distribution range are important in determining the range limits. We comprehensively analysed the influence of recurrent and historic factors and processes on the population genetic structure, mating system and the distribution of genetic variability of the pulmonate freshwater snail Radix balthica. This analysis was based on microsatellite variation and mitochondrial haplotypes using Generalised Linear Statistical Modelling in a Model Selection framework. Results: Populations of R. balthica were found throughout North-Western Europe with range margins marked either by dispersal barriers or the presence of other Radix taxa. Overall, the population structure was characterised by distance independent passive dispersal mainly along a Southwest-Northeast axis, the absence of isolation-by-distance together with rather isolated and genetically depauperated populations compared to the variation present in the entire species due to strong local drift. A recent, climate driven range expansion explained most of the variance in genetic variation, reducing at least temporarily the genetic variability in this area. Other factors such as geographic marginality and dispersal barriers play only a minor role. Conclusions: To our knowledge, such a population structure has rarely been reported before. It might nevertheless be typical for passively dispersed, patchily distributed taxa (e.g. freshwater invertebrates). The strong local drift implied in such a structure is expected to erode genetic variation at both neutral and coding loci and thus probably diminish evolutionary potential. This study shows that the analysis of multiple factors is crucial for the inference of the processes shaping the distribution of genetic variation throughout species ranges. Additional files Additional file 1: Distribution of Radix taxa. Spatial distribution of the Radix MOTU as defined in Pfenninger et al. 2006 plus an additional, newly discovered taxon. This map is the basis for the inference of the species range of R. balthica. Additional file 2: Sampling site table and spatial distribution of diversity indices, selfing estimates and inferred population bottlenecks for R. balthica. Table of sampling site code, geographical position in decimal degrees latitude and longitude, number of individuals analysed with microsatellites (Nnuc), expected heterozygosity (HE) and standard deviation across loci, mean rarefied number of alleles per microsatellite locus (A) and their standard deviation, number of individuals analysed for mitochondrial variation (Nmt), rarefied number of mitochondrial COI haplotypes (Hmt), number of individuals measured for body size (Nsize). Figures A1 - A3 show a graphical representation of the spatial distribution of He, Hmt and, s, respectively. Additional file 3: Assessment of environmental marginality. PCA (principle component analysis) on 35 climatic parameters for the period from 1960 - 2000 from publicly availableWorldClim data. Additional file 4: Inference of a recent climate driven range expansion in R. balthica. Analysis of the freshwater benthos long term monitoring data of the Swedish national monitoring databases at the Swedish University of Agricultural Sciences SLU with canonical correspondence analysis.
Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT00677209
Background: Care management programmes are an effective approach to care for high risk patients with complex care needs resulting from multiple co-occurring medical and non-medical conditions. These patients are likely to be hospitalized for a potentially "avoidable" cause. Nurse-led care management programmes for high risk elderly patients showed promising results. Care management programmes based on health care assistants (HCAs) targeting adult patients with a high risk of hospitalisation may be an innovative approach to deliver cost-efficient intensified care to patients most in need. Methods: PraCMan is a cluster randomized controlled trial with primary care practices as unit of randomisation. The study evaluates a complex primary care practice-based care management of patients at high risk for future hospitalizations. Eligible patients either suffer from type 2 diabetes mellitus, chronic obstructive pulmonary disease, chronic heart failure or any combination. Patients with a high likelihood of hospitalization within the following 12 months (based on insurance data) will be included in the trial. During 12 months of intervention patients of the care management group receive comprehensive assessment of medical and non-medical needs and resources as well as regular structured monitoring of symptoms. Assessment and monitoring will be performed by trained HCAs from the participating practices. Additionally, patients will receive written information, symptom diaries, action plans and a medication plan to improve self-management capabilities. This intervention is addition to usual care. Patients from the control group receive usual care. Primary outcome is the number of all-cause hospitalizations at 12 months follow-up, assessed by insurance claims data. Secondary outcomes are health-related quality of life (SF12, EQ5D), quality of chronic illness care (PACIC), health care utilisation and costs, medication adherence (MARS), depression status and severity (PHQ-9), self-management capabilities and clinical parameters. Data collection will be performed at baseline, 12 and 24 months (12 months post-intervention). Discussion: Practice-based care management for high risk individuals involving trained HCAs appears to be a promising approach to face the needs of an aging population with increasing care demands. Trial registration: Current Controlled Trials ISRCTN56104508
Background: The automation of objectively selecting amino acid residue ranges for structure superpositions is important for meaningful and consistent protein structure analyses. So far there is no widely-used standard for choosing these residue ranges for experimentally determined protein structures, where the manual selection of residue ranges or the use of suboptimal criteria remain commonplace. Results: We present an automated and objective method for finding amino acid residue ranges for the superposition and analysis of protein structures, in particular for structure bundles resulting from NMR structure calculations. The method is implemented in an algorithm, CYRANGE, that yields, without protein-specific parameter adjustment, appropriate residue ranges in most commonly occurring situations, including low-precision structure bundles, multi-domain proteins, symmetric multimers, and protein complexes. Residue ranges are chosen to comprise as many residues of a protein domain that increasing their number would lead to a steep rise in the RMSD value. Residue ranges are determined by first clustering residues into domains based on the distance variance matrix, and then refining for each domain the initial choice of residues by excluding residues one by one until the relative decrease of the RMSD value becomes insignificant. A penalty for the opening of gaps favours contiguous residue ranges in order to obtain a result that is as simple as possible, but not simpler. Results are given for a set of 37 proteins and compared with those of commonly used protein structure validation packages. We also provide residue ranges for 6351 NMR structures in the Protein Data Bank. Conclusions: The CYRANGE method is capable of automatically determining residue ranges for the superposition of protein structure bundles for a large variety of protein structures. The method correctly identifies ordered regions. Global structure superpositions based on the CYRANGE residue ranges allow a clear presentation of the structure, and unnecessary small gaps within the selected ranges are absent. In the majority of cases, the residue ranges from CYRANGE contain fewer gaps and cover considerably larger parts of the sequence than those from other methods without significantly increasing the RMSD values. CYRANGE thus provides an objective and automatic method for standardizing the choice of residue ranges for the superposition of protein structures. Additional files Additional file 1: Dependence of Q on the order parameter rank. The quantity Qi is plotted against the order parameter rank i for 9 different protein structure bundles. Additional file 2: Dependence of P on the clustering stage. The quantity Pi is plotted against the clustering stage i for 9 different protein structure bundles. Additional file 3: Dependence of CYRANGE results on the minimal cluster size parameter my. The sequence coverage (red) and RMSD (blue) of the residue ranges determined by CYRANGE were plotted as a function of my for 9 different protein structure bundles. The dotted vertical line indicates the default value, my = 8. Where CYRANGE found two domains, the RMSD values of the individual domains are shown in light and dark blue. Additional file 4: Dependence of CYRANGE results on the domain boundary extension parameter m. See Additional File 3 for details. Additional file 5: Dependence of CYRANGE results on the minimal gap width g. See Additional File 3 for details. Additional file 6: Dependence of CYRANGE results on the relative RMSD decrease parameter delta. See Additional File 3 for details. Additional file 7: Dependence of CYRANGE results on the absolute RMSD decrease parameter delta abs. See Additional File 3 for details. Additional file 8: Dependence of CYRANGE results on the gap penalty parameter gamma. See Additional File 3 for details. Additional file 9: Correlation between the sequence coverage from CYRANGE, FindCore and PSVS, and the GDT total score, GDT_TS. Each data point represents a protein shown in Figures 3 and 4. The coverage is the percentage of amino acid residues included in the residue ranges found by the different methods. The GDT_TS value is defined by GDT_TS = (P1 + P2 + P4 + P8)/4, where Pd is the fraction of residues that can be superimposed under a distance cutoff of d Å. Additional file 10: Correlation between the RMSD value for the residue ranges from CYRANGE, FindCore and PSVS, and the GDT total score, GDT_TS. Each data point represents one protein domain. See Additional File 9 for details.
Background: Dispersal rates, i.e. the effective number of dispersing individuals per unit time, are the product of dispersal capacity, i.e. a species physiological potential for dispersal, dispersal behaviour, i.e. the decision to leave a habitat patch in favour of another, and connectivity of occupied habitat. Dispersal of species that are highly specialised to a certain habitat is thus strongly limited by habitat availability. Additionally, species inhabiting very stable environments may adopt a sedentary life-style. Both factors should lead to strong genetic differentiation in highly specialised species inhabiting stable environments. These two factors apply to our model species Rhyacophila pubescens a highly specialised freshwater insect that occurs in tufa springs, a very stable habitat. Results: We examined the genetic population structure and phylogeography using range-wide mtCOI sequence and AFLP data from 333 individuals of R. pubescens. We inferred the location of Pleistocene refugia and postglacial colonisation routes of R. pubescens, and examined ongoing local differentiation. Our results indicate intraregional differentiation with a high number of locally endemic haplotypes, that we attributed to habitat specificity and low dispersal rates of R. pubescens. We observed high levels of genetic diversity south of the Alps and genetic impoverishment north of the Alps. Estimates of migrants placed the refugium and the source of the colonisation in the Dauphine Alps (SW Alps). Conclusions: This is the first example of an aquatic insect with a colonisation route along the western margin of the Alps to the Central European highlands. The study also shows that specialisation to a stable environment may have promoted a behavioural shift to decreased dispersal rates, leading to stronger local population differentiation than in less specialised aquatic insects. Alternatively, the occurrence of highly specialised tufa spring habitats may have been more widespread in the past, leading to range regression and fragmentation among present day R. pubescens populations.
Background: Natural history museums receive a rapidly growing number of requests for tissue samples from preserved specimens for DNA-based studies. Traditionally, dried vertebrate specimens were treated with arsenic because of its toxicity and insect-repellent effect. Arsenic has negative effects on in vivo DNA repair enzymes and consequently may inhibit PCR performance. In bird collections, foot pad samples are often requested since the feet were not regularly treated with arsenic and because they are assumed to provide substantial amounts of DNA. However, the actual influence of arsenic on DNA analyses has never been tested. Findings: PCR success of both foot pad and body skin samples was significantly lower in arsenic-treated samples. In general, foot pads performed better than body skin samples. Moreover, PCR success depends on collection date in which younger samples yielded better results. While the addition of arsenic solution to the PCR mixture had a clear negative effect on PCR performance after the threshold of 5.4 μg/μl, such high doses of arsenic are highly unlikely to occur in dried zoological specimens. Conclusions: While lower PCR success in older samples might be due to age effects and/or DNA damage through arsenic treatment, our results show no inhibiting effect on DNA polymerase. We assume that DNA degradation proceeds more rapidly in thin tissue layers with low cell numbers that are susceptible to external abiotic influences. In contrast, in thicker parts of a specimen, such as foot pads, the outermost horny skin may act as an additional barrier. Since foot pads often performed better than body skin samples, the intention to preserve morphologically important structures of a specimen still conflicts with the aim to obtain optimal PCR success. Thus, body skin samples from recently collected specimens should be considered as alternative sources of DNA.
Background: Until recently, read lengths on the Solexa/Illumina system were too short to reliably assemble transcriptomes without a reference sequence, especially for non-model organisms. However, with read lengths up to 100 nucleotides available in the current version, an assembly without reference genome should be possible. For this study we created an EST data set for the common pond snail Radix balthica by Illumina sequencing of a normalized transcriptome. Performance of three different short read assemblers was compared with respect to: the number of contigs, their length, depth of coverage, their quality in various BLAST searches and the alignment to mitochondrial genes. Results: A single sequencing run of a normalized RNA pool resulted in 16,923,850 paired end reads with median read length of 61 bases. The assemblies generated by VELVET, OASES, and SeqMan NGEN differed in the total number of contigs, contig length, the number and quality of gene hits obtained by BLAST searches against various databases, and contig performance in the mt genome comparison. While VELVET produced the highest overall number of contigs, a large fraction of these were of small size (< 200bp), and gave redundant hits in BLAST searches and the mt genome alignment. The best overall contig performance resulted from the NGEN assembly. It produced the second largest number of contigs, which on average were comparable to the OASES contigs but gave the highest number of gene hits in two out of four BLAST searches against different reference databases. A subsequent meta-assembly of the four contig sets resulted in larger contigs, less redundancy and a higher number of BLAST hits. Conclusion: Our results document the first de novo transcriptome assembly of a non-model species using Illumina sequencing data. We show that de novo transcriptome assembly using this approach yields results useful for downstream applications, in particular if a meta-assembly of contig sets is used to increase contig quality. These results highlight the ongoing need for improvements in assembly methodology. Keywords: next generation sequencing; short read assembly; Mollusca