Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity

Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids.

Development of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors

Members of the Arenaviridae are a threat to public health and can cause meningitis and hemorrhagic fever, yet treatment options remain limited by a lack of effective antivirals. In this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) complementary to viral genomic RNA were effective in reducing arenavirus replication in cell cultures and in vivo. PPMO complementary to the Junín virus genome were designed to interfere with viral RNA synthesis, translation, or both. However, only PPMO designed to potentially interfere with translation were effective in reducing virus replication. PPMO complementary to sequence that is highly conserved across arenaviruses and located at the 5’-termini of both genomic segments were effective against Junín, Tacaribe, Pichinde and Lymphocytic Choriomeningitis arenavirus-infected cell cultures, and suppressed viral titers in the livers of LCMV-infected mice. These results suggest that arenavirus 5’-genomic-termini represent promising targets for pan-arenavirus antiviral therapeutic development.

Portfolio-Werbung als Technik des Impression Management: Eine Untersuchung zur gegenseitigen Stärkung von Dachmarke und Produktmarken in komplexen Markenarchitekturen

In recent years, the importance of the corporate brand (e.g. P&G, Nestlé, Unilever) has grown significantly and companies increasingly strive to strengthen their corporate brand. One way to strengthen the corporate brand is portfolio advertisement, in which the corporate brand is presented alongside with several product brands of its portfolio (e.g. VW with its product brands Touareg, Touran, Golf and Polo). The aim of portfolio advertising is to generate a positive image spill-over effect from the product brands onto the corporate brand in order to enhance the consumers’ perceived competence of the corporate brand. In four experimental settings Christian Boris Brunner demonstrates the great potential of portfolio advertising and highlights the risks associated with portfolio advertising in practice. In a first experiment, he compares portfolio advertising with single brand advertisements. Moreover, in case of portfolio advertising he manipulates the fit between the product brands, because the consumer has to establish a logical coherence between the individual brands. However, asconsumers have limited capacity for processing information, special attention should be paid to the number of product brands and to the processing depth of the consumer during confrontation with portfolio advertising. These key factors are taken into consideration in a second extensive experiment involving fictitious corporate and product brands. The effects of portfolio advertising on a product brand are also examined. Furthermore, the strength of product brands, i.e. brand knowledge as well as brand image and consumer’s knowledge of the brands, must be taken into consideration. In a third experiment, both the brand strength of real product brands as well as the fit between product brands are manipulated. Portfolio advertising could also have a positive image spill-over effect when companies introduce a new product brand under the umbrella of the corporate brand while communicating all product brands together. Based on considerations, in a fourth experiment, Christian Boris Brunner shows that portfolio advertising could also have a positive image spill-over effect on a new (unknown) product brand. Concluding his work, Christian Boris Brunner provides implications for future research concerning portfolio advertising as well as the management of a corporate brand in complex brand architectures. Concerning practical implications, these four experiments underline a high relevance to marketing and brand managers, who could increase corporate and product brands’ potential by means of portfolio advertising.

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

Investigating flavonoids as molecular templates for the design of small-molecule inhibitors of cell signaling

Epidemiological and clinical trials reveal compelling evidence for the ability of dietary flavonoids to lower cardiovascular disease risk. The mechanisms of action of these polyphenolic compounds are diverse, and of particular interest is their ability to function as protein and lipid kinase inhibitors. We have previously described structure-activity studies that reinforce the possibility for using flavonoid structures as templates for drug design. In the present study, we aim to begin constructing rational screening strategies for exploiting these compounds as templates for the design of clinically relevant, antiplatelet agents. We used the platelet as a model system to dissect the structural influence of flavonoids, stilbenes, anthocyanidins, and phenolic acids on inhibition of cell signaling and function. Functional groups identified as relevant for potent inhibition of platelet function included at least 2 benzene rings, a hydroxylated B ring, a planar C ring, a C ring ketone group, and a C-2 positioned B ring. Hydroxylation of the B ring with either a catechol group or a single C-4' hydroxyl may be required for efficient inhibition of collagen-stimulated tyrosine phosphorylated proteins of 125 to 130 kDa, but may not be necessary for that of phosphotyrosine proteins at approximately 29 kDa. The removal of the C ring C-3 hydroxyl together with a hydroxylated B ring (apigenin) may confer selectivity for 37 to 38 kDa phosphotyrosine proteins. We conclude that this study may form the basis for construction of maps of flavonoid inhibitory activity on kinase targets that may allow a multitargeted therapeutic approach with analogue counterparts and parent compounds.

Targeting Staphylococcus aureus quorum sensing with non-peptidic small molecule inhibitors

A series of 3-oxo-C12-HSL, tetramic acid and tetronic acid analogues was synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were non-competitive inhibitors of the auto-inducing peptide (AIP)-activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17 which reduced nasal cell colonization and arthritis in a murine infection model.

Der Wissenschaftlichkeit auf der Spur: zum Einsatz von Korpora in der Vermittlung des Deutschen als (fremder) Wissenschaftssprache

Recently, Corpus Linguistics has become a popular research tool in the field of German as a Foreign Language. However, little attention has been paid to teaching and learning potentials that corpora and corpus-based teaching offer. This paper seeks to demonstrate some of the ways in which corpus-based techniques can be used for teaching purposes, even by those who have little experience in Corpus Linguistics. The focus will be on teaching and learning German for Academic Purposes in German Studies abroad.