Comparison of the wound-activated transformation of caulerpenyne by invasive and noninvasive Caulerpa species of the Mediterranean

The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne (1). This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 (9) can be identified by liquid chromatography–mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic , transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species.     

A proxy architecture for collaborative media streaming

Streaming media from the Internet is a successful application for end-users. With the upcoming success of mobile devices and home networking environments, cooperation among users will become more important in the future. To achieve such cooperation, explicit middleware standards have been defined. On the other hand, Internet conferencing applications do not handle collaborative streaming sessions with individual control for each user. We propose a new concept for cooperation exemplary for collaborative media streaming using IETF multimedia session control protocols together with a proxy architecture. This concept enables both synchronization among clients and flexible control to individual users.     

Immortalized gonadotropin-releasing hormone neurons secrete gamma-aminobutyric acid-evidence for an autocrine regulation

The immortalized hypothalamic neuronal cell lines GT1-1 and GT1-7 represent unique model systems to investigate the physiological control of gonadotropin-releasing hormone (GnRH) secretion. Using immunofluorescence microscopy, key proteins of regulated exocytosis, e.g. synaptotagmin, synaptobrevin and SNAP-25 (synaptosomal associated protein of 25 kDa) were found in GT1 neurons. In addition, GT1 neurons contained synaptophysin, a marker protein for small synaptic vesicles (SSVs) which are responsible for the storage of neurotransmitters such as gamma-aminobutyric acid (GABA). Upon subcellular fractionation, a lighter vesicle population characterized by synaptophysin separated from a denser vesicle population containing GnRH. Both vesicle populations contained synaptobrevin and synaptotagmin. Besides GnRH, GT1 neurons expressed glutamic acid decarboxylase at the mRNA-level and synthesized GABA. More importantly, GT1 neurons took up and stored 3H-GABA. The stored GABA was released after stimulation with increasing K+ concentrations and by alpha-latrotoxin. Reducing the extracellular Ca2+-concentration abolished stimulated secretion, indicating that GABA was released by regulated exocytosis. Hormone secretion from GT1 neurons is controlled by GABA via GABA(A) and GABA(B) receptors reflecting the situation in vivo. Our data provide the first evidence that GT1 neurons possess a second regulated secretory pathway sustained by SSVs storing and releasing GABA. The released GABA influences GnRH secretion by an auto- or paracrine loop.     

Systemic aspects of R&D policy subsidies for R&D collaborations and their effects on private R&D

This paper analyses how context- and time-dependent factors determine the impact of R&D subsidies on firm behaviour with respect to private R&D expenditures. Based on German R&D survey data, we combine propensity score matching with a difference-in-difference estimator in order to measure the causal influence of public direct R&D project funding on firm behaviour. Our results indicate that (i) repeated participation in R&D projects on average leads to a higher increase in R&D expenditures than once-off funding; (ii) the aggregate effect of R&D funding on R&D expenditures of business firms is somewhat higher for business–business collaboration projects than for science–business collaboration projects; (iii) R&D expenditures of business firms that cooperate with science show a higher share of external R&D spending. Results of one particular cluster programme indicate that at least the short-term development of R&D does not so much depend on which programme direct R&D project funding is applied to.     

Biological evaluation and structural determinants of p38α mitogen-activated-protein kinase and c-Jun-N-terminal kinase 3 inhibition by flavonoids

A series of 42 naturally occurring flavonoids and one flavonoid glucuronide were tested for their ability to inhibit p38α mitogen-activated protein kinase (p38α) and c-Jun-N-terminal kinase 3 (JNK3). Potent inhibitors with IC(50) values in the low micromolar range were identified. Structure-activity relationships were evaluated and the most promising compounds were docked into the ATP binding site of these kinases. Among the different classes of flavonoids, the flavonol group showed better inhibition of p38α. Of this class, kaempferol-7,4'-dimethylether was a potent p38α inhibitor, displaying 13-fold selectivity for p38α over JNK3. The flavone compounds without a 6-methoxy group preferentially inhibited JNK3. The flavone glycoside, luteolin-7-O-glycoside, was identified as a potent inhibitor with the greatest selectivity toward JNK3. In contrast, the flavanol compounds displayed similar inhibitory activities toward both kinases.     

Synthesis and Biological Testing of N‐Aminoimidazole‐Based p38α MAP Kinase Inhibitors

The p38 mitogen‐activated protein (MAP) kinase α plays a central role in the regulation of cellular responses such as differentiation, proliferation, apoptosis, and inflammation. Inhibition of p38 results in decreased synthesis of pro‐inflammatory cytokines. To date, diverse p38α inhibitors are in phase II clinical trials for numerous cytokine‐dependent diseases. 2‐Sulfanylimidazole derivatives offer advantages over the prototype inhibitor SB 203580, including fewer cytochrome P450 interactions and better kinetic properties. The aim of this study was to develop novel 1,2,4,5‐tetrasubstituted pyridinylimidazoles with acyl residues at the imidazole N1 position that can interact with the kinase's hydrophobic region II (HR II) or sugar pocket (SP) to improve both selectivity and activity. The substitution pattern was optimized by variation of the acyl moiety at the N1 position of the N‐aminoimidazole core. Acylation of the amino function was used for optimization and led to potent p38α MAPK inhibitors.     

Modulation of Aβ42 Aggregation Kinetics and Pathway by Low-Molecular-Weight Inhibitors

The aggregation of amyloid-β 42 (Aβ42) is directly related to the pathogenesis of Alzheimer's disease. Here, we have investigated the early stages of the aggregation process, during which most of the cytotoxic species are formed. Aβ42 aggregation kinetics, characterized by the quantification of Aβ42 monomer consumption, were tracked by real-time solution NMR spectroscopy (RT-NMR) allowing the impact that low-molecular-weight (LMW) inhibitors and modulators exert on the aggregation process to be analysed. Distinct differences in the Aβ42 kinetic profiles were apparent and were further investigated kinetically and structurally by using thioflavin T (ThT) and transmission electron microscopy (TEM), respectively. LMW inhibitors were shown to have a differential impact on early-state aggregation. Insight provided here could direct future therapeutic design based on kinetic profiling of the process of fibril formation.     

Anti-inflammatory activity of American yam Dioscorea trifida L.f. in food allergy induced by ovalbumin in mice

Tropical ecosystems are particularly rich in edible plant species with different bioactive substances. Among the plants with promising benefits for health are species from the genus Dioscorea (Dioscoreaceae), especially those named yam. Recent studies have shown the beneficial effects of different species of Dioscorea, and its main constituent, diosgenine, in the treatment of food allergy. In this study we evaluated the potential of D. trifida, the only yam native from South America, in the treatment of ovalbumin (OVA) induced food allergy in Balb/c mice. HPLC/DAD analysis showed the presence of three very distinctive groups of natural products in extracts and fractions: (I) very polar substances, including allantoin, (II) phenolic substances as flavonoids and phenolic acids and (III) diosgenin and derivatives. Sensitive mice received casein feed with supplementation of crude extract (CE) and fractions. The supplementation with all products from D. trifida reduced IGE, intestinal oedema and mucus production, parameters observed in OVA allergic mice. The results showed the potential of this food to prevent or treat this disease and the necessity to be better explored.     

Preschool executive control on the Shape School task: Measurement considerations and utility.

Executive functions (EF) necessary for purposeful goal-directed activities undergo rapid change and development during the preschool years. However, of the few psychometrically valid measures of EF suitable for use with preschoolers, information on task sensitivity and predictive validity is scant. The neurodevelopmental correlates of early executive difficulties are also largely unknown. In this study, the discriminant and predictive validity of the recently developed Shape School task (Espy, Bull, Martin, & Stroup, 2006) was examined with data from a regional sample of 209 preschool children at age 4 years. A 2-tiered measurement approach was used, with task completion examined in addition to efficiency. Children's performance was also examined in relation to functioning in a range of neurodevelopmental domains. The Shape School task showed some usefulness in capturing expected differences between at-risk and typically developing children. Performance loaded heavily on language and global cognitive abilities. However, several other factors were also implicated, including attention, motor skills, and ocular control. In addition, task completion and efficiency scores appeared to reflect different aspects of performance, and their associations with neurodevelopmental function and later academic achievement on the Woodcock-Johnson Tests of Achievement at age 6 years also differed. Implications for the application of the Shape School task are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Negative Priming Effects in Children Engaged in Nonspatial Tasks: Evidence for Early Development of an Intact Inhibitory Mechanism.

Three experiments are reported that examined conceptual negative priming effects in children 5 to 12 years of age. Experiment 1 used a negative priming variant of a flanker task requiring the naming of a central color blob flanked by irrelevant distractors. Experiment 2 used a negative priming variant of the Stroop color-word task. Experiment 3 used a same-different matching task with novel 3-D shapes. Results revealed significant and equivalent magnitudes of negative priming across the tested age groups for all 3 tasks. It is concluded that the inhibitory mechanism underlying conceptual (i.e., identity or semantic) negative priming in visual selective attention tasks is intact in young children. Because the findings and conclusions diverge from the developmental literature on negative priming, the authors attempt to reconcile the contradictions by pinning down the reasons for the discrepancies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)