610 Medizin und Gesundheit
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- Poecilia mexicana (1)
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- diabetic nephropathy (1)
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Background: The ability to create nanostructures with biomolecules is one of the key elements in nanobiotechnology. One of the problems is the expensive and mostly custom made equipment which is needed for their development. We intended to reduce material costs and aimed at miniaturization of the necessary tools that are essential for nanofabrication. Thus we combined the capabilities of molecular ink lithography with DNA-self-assembling capabilities to arrange DNA in an independent array which allows addressing molecules in nanoscale dimensions.
Results: For the construction of DNA based nanostructures a method is presented that allows an arrangement of DNA strands in such a way that they can form a grid that only depends on the spotted pattern of the anchor molecules. An atomic force microscope (AFM) has been used for molecular ink lithography to generate small spots. The sequential spotting process allows the immobilization of several different functional biomolecules with a single AFM-tip. This grid which delivers specific addresses for the prepared DNA-strand serves as a two-dimensional anchor to arrange the sequence according to the pattern. Once the DNA-nanoarray has been formed, it can be functionalized by PNA (peptide nucleic acid) to incorporate advanced structures.
Conclusions: The production of DNA-nanoarrays is a promising task for nanobiotechnology. The described method allows convenient and low cost preparation of nanoarrays. PNA can be used for complex functionalization purposes as well as a structural element.
Background
In many species males face a higher predation risk than females because males display elaborate traits that evolved under sexual selection, which may attract not only females but also predators. Females are, therefore, predicted to avoid such conspicuous males under predation risk. The present study was designed to investigate predator-induced changes of female mating preferences in Atlantic mollies (Poecilia mexicana). Males of this species show a pronounced polymorphism in body size and coloration, and females prefer large, colorful males in the absence of predators.
Results
In dichotomous choice tests predator-naïve (lab-reared) females altered their initial preference for larger males in the presence of the cichlid Cichlasoma salvini, a natural predator of P. mexicana, and preferred small males instead. This effect was considerably weaker when females were confronted visually with the non-piscivorous cichlid Vieja bifasciata or the introduced non-piscivorous Nile tilapia (Oreochromis niloticus). In contrast, predator experienced (wild-caught) females did not respond to the same extent to the presence of a predator, most likely due to a learned ability to evaluate their predators' motivation to prey.
Conclusions
Our study highlights that (a) predatory fish can have a profound influence on the expression of mating preferences of their prey (thus potentially affecting the strength of sexual selection), and females may alter their mate choice behavior strategically to reduce their own exposure to predators. (b) Prey species can evolve visual predator recognition mechanisms and alter their mate choice only when a natural predator is present. (c) Finally, experiential effects can play an important role, and prey species may learn to evaluate the motivational state of their predators.
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.
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.
The armed conflict in Afghanistan since 2001 has raised manifold questions pertaining to the humanitarian rules relative to the conduct of hostilities. In Afghanistan, as is often the case in so-called asymmetric conflicts, the geographical and temporal boundaries of the battlefield, and the distinction between civilians and fighters, are increasingly blurred. As a result, the risks for both civilians and soldiers operating in Afghanistan are high. The objective of this article is to assess whether - and if so how much - the armed conflict in Afghanistan has affected the application and interpretation of the principles of distinction, proportionality, and precaution - principles that form the core of legal rules pertaining to the conduct of hostilities.