193 research outputs found

    Hydrogels and Their Role in Biosensing Applications

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    Hydrogels play an important role in the field of biomedical research and diagnostic medicine. They are emerging as a powerful tool in the context of bioanalytical assays and biosensing. In this context, this review gives an overview of different hydrogels and the role they adopt in a range of applications. Not only are hydrogels beneficial for the immobilization and embedding of biomolecules, but they are also used as responsive material, as wearable devices, or as functional material. In particular, the scientific and technical progress during the last decade is discussed. The newest hydrogel types, their synthesis, and many applications are presented. Advantages and performance improvements are described, along with their limitations

    Position-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes

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    A series of oligodeoxyribonucleotides and oligoribonucleotides containing single and multiple tricyclo(tc)-nucleosides in various arrangements were prepared and the thermal and thermodynamic transition profiles of duplexes with complementary DNA and RNA evaluated. Tc-residues aligned in a non-continuous fashion in an RNA strand significantly decrease affinity to complementary RNA and DNA, mostly as a consequence of a loss of pairing enthalpy ΔH. Arranging the tc-residues in a continuous fashion rescues Tm and leads to higher DNA and RNA affinity. Substitution of oligodeoxyribonucleotides in the same way causes much less differences in Tm when paired to complementary DNA and leads to substantial increases in Tm when paired to complementary RNA. CD-spectroscopic investigations in combination with molecular dynamics simulations of duplexes with single modifications show that tc-residues in the RNA backbone distinctly influence the conformation of the neighboring nucleotides forcing them into higher energy conformations, while tc-residues in the DNA backbone seem to have negligible influence on the nearest neighbor conformations. These results rationalize the observed affinity differences and are of relevance for the design of tc-DNA containing oligonucleotides for applications in antisense or RNAi therapy

    Expanding the Repertoire of Natural Product-Inspired Ring Pairs for Molecular Recognition of DNA

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    A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the Py/Im polyamide pairing rules

    Cytogenetic characterization of telomeres in the holocentric chromosomes of the lepidopteran Mamestra brassicae

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    Telomeres of the Mamestra brassica holocentric chromosomes were studied by Southern blotting, in-situ hybridization and Bal31 assay evidencing the presence of the telomeric (TTAGG)(n) repeat. Successively, molecular analysis of telomeres showed that TRAS1 transposable elements were present at the subtelomeric regions of autosomes but not in the NOR-bearing telomeres of the Z and W sex chromosomes. TRAS1 appeared to be transcriptionally active and non-methylated, as evaluated by RT-PCR and digestion with MspI and HpaII. Finally, dot-blotting experiments showed that the 2.8 +/- 0.5% of the M. brassicae genome consists of TRAS1

    Design and Synthesis of Heterocyclic Cations for Specific DNA Recognition: From AT-Rich to Mixed-Base-Pair DNA Sequences

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    The compounds synthesized in this research were designed with the goal of establishing a new paradigm for mixed-base-pair DNA sequence-specific recognition. The design scheme starts with a cell-permeable heterocyclic cation that binds to AT base pair sites in the DNA minor groove. Modifications were introduced in the original compound to include an Hbond accepting group to specifically recognize the G-NH that projects into the minor groove. Therefore, a series of heterocyclic cations substituted with an azabenzimidazole ring has been designed and synthesized for mixed-base-pair DNA recognition. The most successful compound, 12a, had an azabenzimidazole to recognize G and additional modifications for general minor groove interactions. It binds to the DNA site −AAAGTTT− more strongly than the −AAATTT− site without GC and indicates the design success. Structural modifications of 12a generally weakened binding. The interactions of the new compound with a variety of DNA sequences with and without GC base pairs were evaluated by thermal melting analysis, circular dichroism, fluorescence emission spectroscopy, surface plasmon resonance, and molecular modeling

    Functional and self-rated health mediate the association between diabetes and depression

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    Depression is common among persons with diabetes and associated with adverse health outcomes. To date, little is known about the causal mechanisms that lead to depression in diabetes. The aim of the present study was to examine to which extent functional and self-rated health mediate the association between physical health and depressive symptoms in diabetes. Data of n = 3222 individuals with type 2 diabetes were analyzed cross-sectionally and longitudinally at three measurement occasions using path analysis. Indicators of physical health were glycemic control, number of comorbid somatic diseases, BMI, and insulin dependence. Furthermore, functional health, self-rated health and depressive symptoms were assessed. The effects of physical health on depressive symptoms were largely mediated by functional health and self-rated health. There was only a weak indirect effect of physical health on depressive symptoms. In contrast, self-rated health was a strong direct predictor of depressive symptoms. Self-rated health in turn depended strongly on patients’ functional health. The way individuals perceive their health appears to have a stronger effect on their depressive symptoms than objective physical indicators of diabetes. Therefore practitioners should be trained to pay more attention to their patients’ subjective health perceptions
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