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Background: Wnt signaling controls the balance between stem cell proliferation and differentiation and body patterning throughout development. Previous data demonstrated that non-canonical Wnts (Wnt5a, Wnt11) increased cardiac gene expression of circulating endothelial progenitor cells (EPC) and bone marrow-derived stem cells cultured in vitro. Since previous studies suggested a contribution of the protein kinase C (PKC) family to the Wnt5a-induced signalling, we investigated which PKC isoforms are activated by non-canonical Wnt5a in human EPC. Methodology/Principal Findings: Immunoblot experiments demonstrated that Wnt5a selectively activated the novel PKC isoform, PKC delta, as evidenced by phosphorylation and translocation. In contrast, the classical Ca2+-dependent PKC isoforms, PKC alpha and beta2, and one of the other novel PKC isoforms, PKC epsilon, were not activated by Wnt5a. The PKC delta inhibitor rottlerin significantly blocked co-culture-induced cardiac differentiation in vitro, whereas inhibitors directed against the classical Ca2+-dependent PKC isoforms or a PKC epsilon-inhibitory peptide did not block cardiac differentiation. In accordance, EPC derived from PKC delta heterozygous mice exhibited a significant reduction of Wnt5a-induced cardiac gene expression compared to wild type mice derived EPC. Conclusions/Significance: These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta.
In its admissibility decision in the Al-Saadoon case the ECtHR held that the United Kingdom had jurisdiction over the applicants, who had been arrested by British forces and kept in a British-run military prison in Iraq. Just before the respective mandate of the Security Council expired on 31 December 2008, the applicants were transferred to Iraqi custody at Iraqi request and thereby exposed to the risk of an unfair trial followed by capital punishment. In this respect, the case resembles the Soering case, although the applicants were, unlike Soering, not on British territory but on occupied Iraqi soil before they were handed over. This aspect raises the question of Iraqi sovereignty as a norm competing with the UK's human rights obligations. The authors trace back the ECtHR's case law concerning the extraterritorial application of the Convention and analyse the UK judgments and the ECtHR's admissibility decision in the Al-Saadoon affair from this angle. Furthermore they consider the doctrinal consequences of the ECHR's extraterritorial effect in cases like Soering and Al-Saadoon, where contracting parties violate guarantees of the Convention by exposing a person within their jurisdiction to a risk of a treatment contrary to these guarantees by a third state. Finally, they test the argument brought forward by the UK that not transferring the applicants would have violated Iraqi sovereignty and establish patterns how the ECtHR and the UK Courts did cope in the past with international law norms potentially competing with the Convention.
Water-filtered infrared-A (wIRA), as a special form of heat radiation with a high tissue penetration and a low thermal load to the skin surface, can improve the healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic effects. wIRA increases tissue temperature (+2.7°C at a tissue depth of 2 cm), tissue oxygen partial pressure (+32% at a tissue depth of 2 cm) and tissue perfusion. These three factors are decisive for a sufficient supply of tissue with energy and oxygen and consequently also for wound healing and infection defense.
wIRA can considerably alleviate pain (without any exception during 230 irradiations) with substantially less need for analgesics (52–69% less in the groups with wIRA compared to the control groups). It also diminishes exudation and inflammation and can show positive immunomodulatory effects. The overall evaluation of the effect of irradiation as well as the wound healing and the cosmetic result (assessed on visual analogue scales) were markedly better in the group with wIRA compared to the control group. wIRA can advance wound healing (median reduction of wound size of 90% in severely burned children already after 9 days in the group with wIRA compared to 13 days in the control group; on average 18 versus 42 days until complete wound closure in chronic venous stasis ulcers) or improve an impaired wound healing (reaching wound closure and normalization of the thermographic image in otherwise recalcitrant chronic venous stasis ulcers) both in acute and in chronic wounds including infected wounds. After major abdominal surgery there was a trend in favor of the wIRA group to a lower rate of total wound infections (7% versus 15%) including late infections following discharge from hospital (0% versus 8%) and a trend towards a shorter postoperative hospital stay (9 versus 11 days).
Even the normal wound healing process can be improved.
The mentioned effects have been proven in six prospective studies, with most of the effects having an evidence level of Ia/Ib.
wIRA represents a valuable therapy option and can generally be recommended for use in the treatment of acute as well as of chronic wounds.
We establish a methodology and present baseline data for a long-term grassy woodland restoration study that commenced in 2007 in two nature reserves (Mulligans Flat, Goorooyarroo (35° 9–13’ S; 149° 9–12’ E)) totalling 1386 ha on the northern boundary of Canberra, in the Australian Capital Territory in south eastern Australia. The experimental infrastructure comprises 96 × 1 ha sites established in Eucalyptus blakelyi / Eucalyptus melliodora dominated woodland. These are being subjected to varying kangaroo grazing pressure and augmentation with logs, while burning treatments are planned. One reserve (Mulligans Flat) has been fenced for feral predator control and contains half the sites, forming a companion experiment to Goorooyarroo. Our baseline floristic study comprised estimates, at the site level, of ground layer biomass, species biomass, ground cover types and soil (0–10 cm) properties. From these data we conclude that the groundlayer vegetation is dominated by Joycea pallida, Austrodanthonia spp., Themeda australis and Aristida ramosa. These grasses varied in abundance according to differences in soil pH, phosphorus and to a lesser extent nitrates. Forb frequencies were highly sensitive to nitrate levels with annual exotic forbs dominating at high nitrate sites. More generally, soil nutrient levels and exotic species in some sites indicated areas of previous pasture improvement activities. Biomass estimates indicated extremely high grazing pressure, sufficient to negatively affect the habitat quality for ground-dependent fauna and some soil processes. These data will provide an important basis for examining rates of ecosystem recovery under different restoration strategies.
For a virtual screening study, we introduce a combination of machine learning techniques, employing a graph kernel, Gaussian process regression and clustered cross-validation. The aim was to find ligands of peroxisome-proliferator activated receptor gamma (PPAR-y). The receptors in the PPAR family belong to the steroid-thyroid-retinoid superfamily of nuclear receptors and act as transcription factors. They play a role in the regulation of lipid and glucose metabolism in vertebrates and are linked to various human processes and diseases. For this study, we used a dataset of 176 PPAR-y agonists published by Ruecker et al. ...
Two methods for the fast, fragment-based combinatorial molecule assembly were developed. The software COLIBREE® (Combinatorial Library Breeding) generates candidate structures from scratch, based on stochastic optimization [1]. Result structures of a COLIBREE design run are based on a fixed scaffold and variable linkers and side-chains. Linkers representing virtual chemical reactions and side-chain building blocks obtained from pseudo-retrosynthetic dissection of large compound databases are exchanged during optimization. The process of molecule design employs a discrete version of Particle Swarm Optimization (PSO) [2]. Assembled compounds are scored according to their similarity to known reference ligands. Distance to reference molecules is computed in the space of the topological pharmacophore descriptor CATS [3]. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor (PPAR gamma) selective agonists. In a second approach, we developed the formal grammar Reaction-MQL [4] for the in silico representation and application of chemical reactions. Chemical transformation schemes are defined by functional groups participating in known organic reactions. The substructures are specified by the linear Molecular Query Language (MQL) [5]. The developed software package contains a parser for Reaction-MQL-expressions and enables users to design, test and virtually apply chemical reactions. The program has already been used to create combinatorial libraries for virtual screening studies. It was also applied in fragmentation studies with different sets of retrosynthetic reactions and various compound libraries.
Hexham Swamp (32° 52’ S, 151° 41’ E), the largest wetland on the floodplain of the lower Hunter River, New South Wales (ca. 2500 ha in area), historically supported extensive areas of estuarine wetlands. Substantial vegetation changes have occurred following the 1971 construction of floodgates on the main creek draining the swamp. Previous areas of mangroves have been reduced from180 ha to 11 ha, and saltmarsh from 681 ha to 58 ha. Phragmites australis reedswamp has expanded from 170 ha to 1005 ha. Much of the mangrove loss (ca. 130 ha) was a result of clearing, and the remainder has gradually died off. The factors contributing to the dieback are likely to be a combination of drying of the soil, and, at times, waterlogging. Field sampling indicates that a reduction in soil salinity has been an important factor initiating successional change from saltmarsh to Phragmites reedswamp. The data also suggest that increased waterlogging has been an important factor in vegetation change. The initial effect of the floodgates was expected to have been a drying of the swamp, followed over time by an increasing wetness(floodgates and associated drainage are generally intended to reduce the flooding of wetlands). The apparently paradoxical result is likely to have resulted from occlusion of drainage lines by sediment and reeds.
A vegetation survey was undertaken within Columbey National Park (32° 35’S, 151° 44’E) near Clarence Town in the lower Hunter Valley of New South Wales. Multivariate cluster analysis and non-metric multi-dimensional scaling were carried out on plot-based data to classify the vegetation into twelve native communities (one plantation), and each compared with a larger regional dataset. A vegetation map was also prepared, based heavily on extensive ground-data supplemented with aerial photographic interpretation. Although small in size, this reserve conserves good examples of the endangered Lower Hunter Spotted Gum-Ironbark Forest (475 ha) and River-Flat Eucalypt Forest on Coastal Floodplains (124 ha), together with a small parcel of Hunter Lowlands Redgum Forest (3.7 ha). Collectively, these Endangered Ecological Communities occupy approximately 70% of the 870 ha reserve. Small populations of the threatened and previously unreserved orchid, Pterostylis chaetophora are present in the reserve, together with the Endangered Corybas dowlingii and the regionally significant cycad, Macrozamia flexuosa. An historical record of Eucalyptus glaucina could not be substantiated during the current survey, and may have been recorded in error. A total of 349 vascular plant taxa were recorded, including 25 weed species. The vegetation present within Columbey National Park bears strong resemblance to that in the Cessnock region of the Hunter Valley (Bell 2004; DECC 2008), a feature attributed to similar rainfall and soil types. Vegetation communities common between the two areas include Lower Hunter Spotted Gum – Ironbark Forest, Red Ironbark Scrub-Forest, Paperbark Soak Forest, Floodplain Redgum-Box Forest and Gully Rainforest. Unlike the Cessnock area, however, Columbey has not been subject to illegal rubbish dumping to any great degree.