The ABCG1 protein is centrally involved in reverse cholesterol transport from the vessel wall. Investigation of the effects of ABCG1 overexpression or knockdown in vivo has produced controversial results and strongly depended on the gene intervention model in which it was studied. Therefore, we investigated the effect of local overexpression of human ABCG1 in a novel model of vessel wall-directed adenoviral gene transfer in atherosclerotic rabbits. We conducted local, vascular-specific gene transfer by adenoviral delivery of human ABCG1 (Ad-ABCG1-GFP) in cholesterol-fed atherosclerotic rabbits in vivo. Endothelial overexpression of ABCG1 markedly reduced atheroprogression (plaque size) and almost blunted vascular inflammation, as shown by markedly reduced macrophage and smooth muscle cell invasion into the vascular wall. Also endothelial function, as determined by vascular ultrasound in vivo, was improved in rabbits after gene transfer with Ad-ABCG1-GFP. Therefore, both earlier and later stages of atherosclerosis were improved in this model of somatic gene transfer into the vessel wall. In contrast to results in transgenic mice, over-expression of ABCG1 by somatic gene transfer to the atherosclerotic vessel wall results in a significant improvement of plaque morphology and composition, and of vascular function in vivo.

Sprouty-related proteins with EVH1 (enabled/vasodilatorstimulated phosphoprotein homology 1) domain (SPREDs) are inhibitors of MAPK signaling. To elucidate SPRED2 in vivo function, we characterized body homeostasis in SPRED2 ؊/؊ mice. They showed a doubled daily water uptake, induced by elevated serum osmolality, originating from increased blood salt load. Accordingly, serum aldosterone was doubled, accompanied by augmented adrenal aldosterone synthase (AS) expression. Surprisingly, serum vasopressin (AVP) was unaltered, and, as evidenced by halved angiotensin II (Ang II) levels, the renin angiotensin system (RAS) was down-regulated. Adrenocorticotropic hormone (ACTH) was significantly elevated in SPRED2 ؊/؊ mice, together with its secretagogue corticotropinreleasing hormone (CRH) and its downstream target corticosterone. ERK phosphorylation in brains was augmented, and hypothalamic CRH mRNA levels were elevated, both contributing to the increased CRH release. Our data were supported by CRH promoter reporter assays in hypothalamic mHypoE-44 cells, revealing a SPRED-dependent inhibition of Ets (ERK/Etwenty-six)-dependent transcription. Furthermore, SPRED suppressed CRH production in these cells. In conclusion, our study suggests that SPRED2 deficiency leads to an increased MAPK signaling, which results in an augmented CRH promoter activity. The subsequent CRH overproduction causes an up-regulation of downstream hypothalamic-pituitary-adrenal (HPA) hormone secretion. This constitutes a possible trigger for the observed compulsive grooming in SPRED2 ؊/؊ mice and may, together with hyperplasia of aldosterone-producing cells, contribute to the hyperaldosteronism and homeostatic imbalances.

The design of flexible sensors which can be incorporated in textile structures is of decisive importance for the future development of wearables. In addition to their technical functionality, the materials chosen to construct the sensor should be nontoxic, affordable, and compatible with future recycling. Conductive fibres were produced by incorporation of carbon black into regenerated cellulose fibres. By incorporation of 23 wt.% and 27 wt.% carbon black, the surface resistance of the fibres reduced from 1.3 × 1010 Ω·cm for standard viscose fibres to 2.7 × 103 and 475 Ω·cm, respectively. Fibre tenacity reduced to 30–50% of a standard viscose; however, it was sufficient to allow processing of the material in standard textile operations. A fibre blend of the conductive viscose fibres with polyester fibres was used to produce a needle-punched nonwoven material with piezo-electric properties, which was used as a pressure sensor in the very low pressure range of 400–1000 Pa. The durability of the sensor was demonstrated in repetitive load/relaxation cycles. As a regenerated cellulose fibre, the carbon-black-incorporated cellulose fibre is compatible with standard textile processing operations and, thus, will be of high interest as a functional element in future wearables.

Rectal temperature measurement (RTM) from crime scenes is an important parameter for temperature-based time of death estimation (TDE). Various influential variables exist in TDE methods like the uncertainty in thermal and environmental parameters. Although RTM depends in particular on the location of measurement position, this relationship has never been investigated separately. The presented study fills this gap using Finite Element (FE) simulations of body cooling. A manually meshed coarse human FE model and an FE geometry model developed from the CT scan of a male corpse are used for TDE sensitivity analysis. The coarse model is considered with and without a support structure of moist soil. As there is no clear definition of ideal rectal temperature measurement location for TDE, possible variations in RTM location (RTML) are considered based on anatomy and forensic practice. The maximum variation of TDE caused by RTML changes is investigated via FE simulation. Moreover, the influence of ambient temperature, of FE model change and of the models positioning on a wet soil underground are also discussed. As a general outcome, we notice that maximum TDE deviations of up to ca. 2-3 h due to RTML deviations have to be expected. The direction of maximum influence of RTML change on TDE generally was on the line caudal to cranial.

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