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The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
The fear that with the existence of an unconditional basic income sufficient for living many people would cease to engage in a productive life, would only relax, consume and devote to having fun, can be addressed from different perspectives. One of these is the sociology of religion, which allows elaborating the argument that with such a way of life the question about the meaning of life cannot be answered. But this "meaning question", the whole research within the field of the sociology of religion speaks for this, compellingly must be answered by each life praxis. It cannot remain unanswered, as is said already in the Bible: "Man does not live on bread alone, [but on every word that comes from the mouth of God.]" (5. Moses 8.3, Matthew 4.4, Lukas 4.4) The paper examines the reasons of this fact and its consequences in regard to a life with an unconditional basic income sufficient for living.
This paper shows that several typologically unrelated languages share the tendency to avoid voiced sibilant affricates. This tendency is explained by appealing to the phonetic properties of the sounds, and in particular to their aerodynamic characteristics. On the basis of experimental evidence it is shown that conflicting air pressure requirements for maintaining voicing and frication are responsible for the avoidance of voiced affricates. In particular, the air pressure released from the stop phase of the affricate is too high to maintain voicing, which in consequence leads to a devoicing of the frication part.
Our study is concerned with the identification of ‘difficult’ structure s in the acquisition of a foreign language, which will shed light on theoretical considerations of L2 processing. We argue that – compared to simple vocabulary items or abstract syntactic patterns – structures that contain lexical material as well as categorial variables are especially difficult to acquire. The difficulty level for particular patterns is shown to depend on surface invariability but not on the syntactic categories within which target patterns are embedded. As an example we study the distribution of certain structures which are underused by L2 German learners.
The floristic composition and environmental relations of wetland vegetation in the Wallis Lake catchment (32˚ 09’S; 152˚ 20’E), area 1292 km2, on the lower North Coast of NSW are described. The catchment supports wetlands listed as Endangered Ecological Communities (NSW Threatened Species Conservation Act 1995) and plant species of high conservation value. A methodology of air photo interpretation, site-based sampling (114 quadrats) and landscape differentiation was developed. A total of 393 vascular plant taxa were recorded (including 10% exotics). Wetland vegetation formations and subformations including mangrove forest, swamp sclerophyll forest, wet heathland, chenopod shrubland, tussock grassland, sedgeland and rushland are described using numerical classification. 31 plant species of national or regional conservation significance are identified. Four Endangered Ecological Communities are discussed – Coastal Saltmarsh, Swamp Oak Floodplain Forest, Swamp Sclerophyll Forest on Coastal Floodplains, and Freshwater Wetlands on Coastal Floodplains. A key recommendation is the completion of reliable wetland vegetation and soil landscape mapping for all land tenures in the catchment – to assess wetland condition and conservation significance, and representation in formal conservation reserves, thereby directing future priorities for the protection of wetland biodiversity on both public and private lands. The methodology developed can be applied to the survey and conservation of wetland biodiversity in other parts of coastal NSW.
Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances
(2008)
Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone.
Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised controlled study in humans.
Methods: The penetration profiles of the hydrophilic dye fluorescein and the lipophilic dye curcumin in separate standard water-in-oil emulsions were determined on the inner forearm of test persons by tape stripping in combination with spectroscopic measurements. Additionally, the penetration was investigated in vivo by laser scanning microscopy. Transepidermal water loss, hydration of the epidermis, and surface temperature were determined. Three different procedures (modes A, B, C) were used in a randomised order on three separate days of investigation in each of 12 test persons. In mode A, the two dyes were applied on different skin areas without water-filtered infrared-A (wIRA) irradiation. In mode B, the skin surface was irradiated with wIRA over 30 min before application of the two dyes (Hydrosun® radiator type 501, 10 mm water cuvette, orange filter OG590, water-filtered spectrum: 590–1400 nm with dominant amount of wIRA). In mode C, the two dyes were applied and immediately afterwards the skin was irradiated with wIRA over 30 min. In all modes, tape stripping started 30 min after application of the formulations. Main variable of interest was the ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum.
Results: The penetration profiles of the hydrophilic fluorescein showed in case of pretreatment or treatment with wIRA (modes B and C) an increased penetration depth compared to the non-irradiated skin (mode A): The ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum showed medians and interquartile ranges for mode A of 0.017 (0.007/0.050), for mode B of 0.084 (0.021/0.106), for mode C of 0.104 (0.069/0.192) (difference between modes: p=0.0112, significant; comparison mode A with mode C: p<0.01, significant). In contrast to fluorescein, the lipophilic curcumin showed no differences in the penetration kinetics, in reference to whether the skin was irradiated with wIRA or not. These effects were confirmed by laser scanning microscopy. Water-filtered infrared-A irradiation increased the hydration of the stratum corneum: transepidermal water loss rose from approximately 8.8 g m-2 h-1 before wIRA irradiation to 14.2 g m-2 h-1 after wIRA irradiation and skin hydration rose from 67 to 87 relative units. Skin surface temperature increased from 32.8°C before wIRA to 36.4°C after wIRA irradiation.
Discussion: The better penetration of the hydrophilic dye fluorescein after or during skin irradiation (modes B and C) can be explained by increased hydration of the stratum corneum by irradiation with wIRA.
Conclusions: As most topically applied substances for the treatment of patients are mainly hydrophilic, wIRA can be used to improve the penetration of substances before or after application of substances – in the first case even of thermolabile substances – with a broad clinical relevance as a contact free alternative to an occlusive dressing.
Dan Janzen proposed in a paper in 1977 (loc. cit.), that a clone of aphids and for that matter dandelions consists, respectively, of one large ‘super-organism’. In effect a single evolutionary individual able to exploit resources over an expanded geographical range, and sometimes with aphids also, a wider range of resources (different kinds of host plants), much more than if the organism concerned were a single individual. Such a view is of course based on the notion that an asexual lineage (clone) has strict genetic fidelity, that is to say, is genetically identical over its entire genome between clone mates. This seems a highly unlikely scenario and indeed, modern molecular markers have revealed a plethora of mutational events within such so-called clones. Here in this talk I provide evidence from aphids that they are not ‘perfect forms’ but rather show a range of variations, including evidence of hybridization events, and that they can and do adapt to environmental circumstances, sometimes swiftly. Hence that even as asexual lineages, aphids are able to exploit new ecological circumstances and flourish, e.g. host adapted forms, whilst some species, notably the highly polyphagous peach-potato aphid (Myzus persicae), have also evolved resistance to a range of pesticides, and by so doing, have managed to survive in the face of these poisons. However, there are fitness costs associated with such adaptation, more especially in the highly resistant aphids. Because of the variation and adaptation shown by particular aphid species and asexual lineages, they cannot be described as a single evolutionary unit in a ‘Janzenian’ sense. What they show is ecological plasticity and an ability to adapt quickly, in large part enhanced by their incredible rate of reproduction and population expansion. Some migrating winged aphids are constrained in their exploitation of new habitats by environmental factors – geographical, climatic and ecological, especially lack of suitable hosts. In contrast, some other aphid species have seemingly colonized large areas of the world (probably aided by human agency) so that deciding what a population is exactly is a difficult task. It may even be that certain ‘super clones’ detected using molecular markers have indeed spread far and wide, clones which appear to fit the description of being ‘general purpose genotypes’ in that they can feed on a range of plant hosts under a range of different geographical-climatic conditions. As such, they are nearest to Dan Janzen’s views, although here again, strict genetic fidelity is not necessarily proven, only accepted from the application of a limited number of markers, e.g. multilocus genotypes in the case of microsatellite markers.