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Background
More than in other domains the heterogeneous services world in bioinformatics demands for a methodology to classify and relate resources in a both human and machine accessible manner. The Semantic Web, which is meant to address exactly this challenge, is currently one of the most ambitious projects in computer science. Collective efforts within the community have already led to a basis of standards for semantic service descriptions and meta-information. In combination with process synthesis and planning methods, such knowledge about types and services can facilitate the automatic composition of workflows for particular research questions.
Results
In this study we apply the synthesis methodology that is available in the Bio-jETI workflow management framework for the semantics-based composition of EMBOSS services. EMBOSS (European Molecular Biology Open Software Suite) is a collection of 350 tools (March 2010) for various sequence analysis tasks, and thus a rich source of services and types that imply comprehensive domain models for planning and synthesis approaches. We use and compare two different setups of our EMBOSS synthesis domain: 1) a manually defined domain setup where an intuitive, high-level, semantically meaningful nomenclature is applied to describe the input/output behavior of the single EMBOSS tools and their classifications, and 2) a domain setup where this information has been automatically derived from the EMBOSS Ajax Command Definition (ACD) files and the EMBRACE Data and Methods ontology (EDAM). Our experiments demonstrate that these domain models in combination with our synthesis methodology greatly simplify working with the large, heterogeneous, and hence manually intractable EMBOSS collection. However, they also show that with the information that can be derived from the (current) ACD files and EDAM ontology alone, some essential connections between services can not be recognized.
Conclusions
Our results show that adequate domain modeling requires to incorporate as much domain knowledge as possible, far beyond the mere technical aspects of the different types and services. Finding or defining semantically appropriate service and type descriptions is a difficult task, but the bioinformatics community appears to be on the right track towards a Life Science Semantic Web, which will eventually allow automatic service composition methods to unfold their full potential.
Many organisms have developed defences to avoid predation by species at higher trophic levels. The capability of primary producers to defend themselves against herbivores affects their own survival, can modulate the strength of trophic cascades and changes rates of competitive exclusion in aquatic communities. Algal species are highly flexible in their morphology, growth form, biochemical composition and production of toxic and deterrent compounds. Several of these variable traits in phytoplankton have been interpreted as defence mechanisms against grazing. Zooplankton feed with differing success on various phytoplankton species, depending primarily on size, shape, cell wall structure and the production of toxins and deterrents. Chemical cues associated with (i) mechanical damage, (ii) herbivore presence and (iii) grazing are the main factors triggering induced defences in both marine and freshwater phytoplankton, but most studies have failed to disentangle the exact mechanism(s) governing defence induction in any particular species. Induced defences in phytoplankton include changes in morphology (e.g. the formation of spines, colonies and thicker cell walls), biochemistry (such as production of toxins, repellents) and in life history characteristics (formation of cysts, reduced recruitment rate). Our categorization of inducible defences in terms of the responsible induction mechanism provides guidance for future work, as hardly any of the available studies on marine or freshwater plankton have performed all the treatments that are required to pinpoint the actual cue(s) for induction. We discuss the ecology of inducible defences in marine and freshwater phytoplankton with a special focus on the mechanisms of induction, the types of defences, their costs and benefits, and their consequences at the community level.
Fusarium spp. infection of cereal grain is a common problem, which leads to a dramatic loss of grain quality. The aim of the present study was to investigate the effect of Fusarium infection on the wheat storage protein gluten and its fractions, the gliadins and glutenins, in an in vitro model system. Gluten proteins were digested by F. graminearum proteases for 2, 4, 8 and 24 h, separated by Osborne fractionation and characterised by chromatographic (RP-HPLC) and electrophoretic analysis (SDS-Page). Gluten digestion by F. graminearum proteases showed in comparison with gliadins a preference for the glutenins whereas the HMW subfraction was at most affected. In comparison with a untreated control, the HMW subfraction was degraded of about 97% after 4 h incubation with Fusarium proteases. Separate digestion of gliadin and glutenin underlined the preference for HMW-GS. Analogue to the observed change in the gluten composition, the yield of the proteins extracted changed. A higher amount of glutenin fragments was found in the gliadin extraction solution after digestion and could mask a gliadin destruction at the same time. This observation can contribute to explain the frequently reported reduced glutenin amount parallel to an increase in gliadin quantity after Fusarium infection in grains.
Background
Riociguat is the first of a new class of drugs, the soluble guanylate cyclase (sGC) stimulators. Riociguat has a dual mode of action: it sensitizes sGC to the body’s own NO and can also increase sGC activity in the absence of NO. The NO-sGC-pathway is impaired in many cardiovascular diseases such as heart failure, pulmonary hypertension and diabetic nephropathy (DN). DN leads to high cardiovascular morbidity and mortality. There is still a high unmet medical need. The urinary albumin excretion rate is a predictive biomarker for these clinical events. Therefore, we investigated the effect of riociguat, alone and in combination with the angiotensin II receptor antagonist (ARB) telmisartan on the progression of DN in diabetic eNOS knock out mice, a new model closely resembling human pathology.
Methods
Seventy-six male eNOS knockout C57BL/6J mice were divided into 4 groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), riociguat (3 mg/kg), riociguat+telmisartan (3 and 1 mg/kg), and vehicle. Fourteen mice were used as non-diabetic controls. After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were highly increased and similar in all diabetic groups.
Results
Riociguat, alone (105.2 ± 2.5 mmHg; mean±SEM; n = 14) and in combination with telmisartan (105.0 ± 3.2 mmHg; n = 12), significantly reduced blood pressure versus diabetic controls (117.1 ± 2.2 mmHg; n = 14; p = 0.002 and p = 0.004, respectively), whereas telmisartan alone (111.2 ± 2.6 mmHg) showed a modest blood pressure lowering trend (p = 0.071; n = 14). The effects of single treatment with either riociguat (97.1 ± 15.7 µg/d; n = 13) or telmisartan (97.8 ± 26.4 µg/d; n = 14) did not significantly lower albumin excretion on its own (p = 0.067 and p = 0.101, respectively). However, the combined treatment led to significantly lower urinary albumin excretion (47.3 ± 9.6 µg/d; n = 12) compared to diabetic controls (170.8 ± 34.2 µg/d; n = 13; p = 0.004), and reached levels similar to non-diabetic controls (31.4 ± 10.1 µg/d, n = 12).
Conclusion
Riociguat significantly reduced urinary albumin excretion in diabetic eNOS knock out mice that were refractory to treatment with ARB’s alone. Patients with diabetic nephropathy refractory to treatment with ARB’s have the worst prognosis among all patients with diabetic nephropathy. Our data indicate that additional stimulation of sGC on top of standard treatment with ARB`s may offer a new therapeutic approach for patients with diabetic nephropathy resistant to ARB treatment.
Due to their optical and electro-conductive attributes, carbazole derivatives are interesting materials for a large range of biosensor applications. In this study, we present the synthesis routes and fluorescence evaluation of newly designed carbazole fluorosensors that, by modification with uracil, have a special affinity for antiretroviral drugs via either Watson–Crick or Hoogsteen base pairing. To an N-octylcarbazole-uracil compound, four different groups were attached, namely thiophene, furane, ethylenedioxythiophene, and another uracil; yielding four different derivatives. Photophysical properties of these newly obtained derivatives are described, as are their interactions with the reverse transcriptase inhibitors such as abacavir, zidovudine, lamivudine and didanosine. The influence of each analyte on biosensor fluorescence was assessed on the basis of the Stern–Volmer equation and represented by Stern–Volmer constants. Consequently we have demonstrated that these structures based on carbazole, with a uracil group, may be successfully incorporated into alternative carbazole derivatives to form biosensors for the molecular recognition of antiretroviral drugs.
Saccades move objects of interest into the center of the visual field for high-acuity visual analysis. White, Stritzke, and Gegenfurtner (Current Biology, 18, 124–128, 2008) have shown that saccadic latencies in the context of a structured background are much shorter than those with an unstructured background at equal levels of visibility. This effect has been explained by possible preactivation of the saccadic circuitry whenever a structured background acts as a mask for potential saccade targets. Here, we show that background textures modulate rates of microsaccades during visual fixation. First, after a display change, structured backgrounds induce a stronger decrease of microsaccade rates than do uniform backgrounds. Second, we demonstrate that the occurrence of a microsaccade in a critical time window can delay a subsequent saccadic response. Taken together, our findings suggest that microsaccades contribute to the saccadic facilitation effect, due to a modulation of microsaccade rates by properties of the background.
Indirect resource competition and interference are widely occurring mechanisms of interspecific interactions. We have studied the seasonal expression of these two interaction types within a two-species, boreal small mammal system. Seasons differ by resource availability, individual breeding state and intraspecific social system. Live-trapping methods were used to monitor space use and reproduction in 14 experimental populations of bank voles Myodes glareolus in large outdoor enclosures with and without a dominant competitor, the field vole Microtus agrestis. We further compared vole behaviour using staged dyadic encounters in neutral arenas in both seasons. Survival of the non-breeding overwintering bank voles was not affected by competition. In the spring, the numbers of male bank voles, but not of females, were reduced significantly in the competition populations. Bank vole home ranges expanded with vole density in the presence of competitors, indicating food limitation. A comparison of behaviour between seasons based on an analysis of similarity revealed an avoidance of costly aggression against opponents, independent of species. Interactions were more aggressive during the summer than during the winter, and heterospecific encounters were more aggressive than conspecific encounters. Based on these results, we suggest that interaction types and their respective mechanisms are not either–or categories and may change over the seasons. During the winter, energy constraints and thermoregulatory needs decrease direct aggression, but food constraints increase indirect resource competition. Direct interference appears in the summer, probably triggered by each individual’s reproductive and hormonal state and the defence of offspring against conspecific and heterospecific intruders. Both interaction forms overlap in the spring, possibly contributing to spring declines in the numbers of subordinate species.
Restoration of semi-natural grassland communities
involves a combination of (1) sward disturbance to
create a temporal window for establishment, and (2)
target species introduction, the latter usually by seed
sowing. With great regularity, particular species
establish only poorly. More reliable establishment
could improve outcome of restoration projects and
increase cost-effectiveness. We investigated the
abiotic germination niche of ten poorly establishing
calcareous grassland species by simultaneously
exploring the effects of moisture and light availability
and temperature fluctuation on percentage germina-
tion and speed of germination. We also investigated
the effects of three different pre-treatments used to
enhance seed germination – cold-stratification, osmo-
tic priming and priming in combination with gibberellic
acid (GA 3 ) – and how these affected abiotic
germination niches. Species varied markedly in width
of abiotic germination niche, ranging from Carex flacca
with very strict abiotic requirements, to several species
reliably germinating across the whole range of abiotic
conditions. Our results suggest pronounced differ-
ences between species in gap requirements for
establishment. Germination was improved in most
species by at least one pre-treatment. Evidence for
positive effects of adding GA 3 to seed priming
solutions was limited. In several species, pre-treated
seeds germinated under a wider range of abiotic
conditions than untreated seeds. Improved knowledge
of species-specific germination niches and the effects
of seed pre-treatments may help to improve species
establishment by sowing, and to identify species for
which sowing at a later stage of restoration or
introduction as small plants may represent a more
viable strategy.
We show that the residue density of the logarithm of a generalized Laplacian on a closed manifold defines an invariant polynomial-valued differential form. We express it in terms of a finite sum of residues of
classical pseudodifferential symbols. In the case of the square of a Dirac operator, these formulas provide a pedestrian proof of the Atiyah–Singer formula for a pure Dirac operator in four dimensions and for a
twisted Dirac operator on a flat space of any dimension. These correspond to special cases of a more general formula by Scott and Zagier. In our approach, which is of perturbative nature, we use either a Campbell–Hausdorff formula derived by Okikiolu or a noncommutative Taylor-type formula.