18 research outputs found
The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1 alpha
The circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show
that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor
(HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1a via its tail region. Subsequently, CRY1 reduces HIF-1a half-life and binding of HIFs to target gene promoters.
This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the
hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and
migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout.
Altogether, our study provides a mechanistic explanation for genetic association studies linking a
disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis
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Personalised ankle-foot orthoses design based on reverse engineering
Drop Foot (DF) and Food Drop Ă an interchangeable term that describes an abnormal neuromuscular disorder that affects the patient's ability to raise their foot at the ankle. Ankle-Foot Orthoses (AFOs) are devices intended to assist or to restore the motions of the ankle-foot complex. In this paper, personalised AFO development which is based on 3D models of the patient's ankle-foot complex is introduced. Methods of reconstructing 3D models of the ankle-foot based on Reverse Engineering were fully investigated from which the new personalised AFOs were proposed. These AFOs were designed to assist the ankle flexion-extension for DF patients