Hypoxia-inducible factors are the key elements in the essential process of oxygen homeostasis of vertebrate cells. Stabilisation and subsequent nuclear localisation of HIF-alpha subunits results in the activation of target genes such as vegf, epo and glut1. The passage of transcription factors e.g. HIF-1alpha into the nucleus through the nuclear pore complex is regulated by nuclear transport receptors. Therefore nucleocytoplasmic shuttling can regulate transcriptional activity by facilitating the cellular traffic of transcription factors between both compartments. Here, we report on the identification of specific interactions of hypoxia-inducible factors with nuclear transport receptors importin alpha/beta. HIF-1alpha, -1beta, and HIF-2alpha are binding to importin alpha1, alpha3, alpha5, and alpha7. The direct interaction of HIF-1alpha to alpha importins is dependent on a functional nuclear localisation signal within the C-terminal region of the protein. In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors.
The performance of a transparent absorbent adhesive wound dressing (TAAWD) was observed over 7 days in five plastic surgery clinics across Germany. The study included 47 diverse postoperative linear wounds and donor sites with dry or minimal exudate levels. Data on ease of application and removal, adhesive strength, skin compatibility, conformability to the body, visual wound inspection and parameters of wound assessment were collected and analysed. At the end of the observation period, 100% of wounds were recorded as healing with no reported complications. Clinicians considered that the new dressing had predominantly met clinical needs in 89% of cases. The dressing was shown to be skin friendly, easy to apply, adhere and conform to the skin while protecting the wound and allowing the patient to shower. Due to its transparency, the dressing enabled direct wound surveillance without potential disruption to the wound and healing process.
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