Risk factors predictive of adverse drug events and drug-related falls in aged care residents: secondary analysis from the ReMInDAR trial.

Background: Residents of aged-care facilities have high rates of adverse drug events. This study aimed to identify risk factors for adverse drug events in aged-care residents.

Method: This was a secondary study using data from a multicentre randomised controlled trial.

Differences in hydroxylation and binding of Notch and HIF-1alpha demonstrate substrate selectivity for factor inhibiting HIF-1 (FIH-1).

FIH-1, factor inhibiting hypoxia-inducible factor-1 (HIF-1), regulates oxygen sensing by hydroxylating an asparagine within HIF-alpha. It also hydroxylates asparagines in many proteins containing ankyrin repeats, including Notch1-3, p105 and I?B?. Relative binding affinity and hydroxylation rate are crucial determinants of substrate selection and modification.

Activation of HIF-1alpha in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway.

Accumulation of HIF-1alpha during normoxic conditions at high cell density has previously been shown to occur and can be used to stabilize HIF-1alpha protein in the absence of a specific anaerobic chamber. However, the impact and origin of this pool of HIF-1alpha, obtained under normoxia, has been underestimated. In this study, we have systematically compared the related pools of HIF-1alpha stabilized in normoxia by high cell density to those obtained at low density in hypoxia.

Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways.

Cells adapt to hypoxia by a cellular response, where hypoxia-inducible factor 1alpha (HIF-1alpha) becomes stabilized and directly activates transcription of downstream genes. In addition to this "canonical" response, certain aspects of the pathway require integration with Notch signaling, i.e.

HIF-1: master and commander of the hypoxic world. A pharmacological approach to its regulation by siRNAs.

The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O2 level, which is essential for their viability. It is important that this critical transcription factor be tightly regulated in order for cells to respond to a wide range of O2 concentrations. HIF-1 regulation by post-translational modification is the central theme of the scenario of O2 homeostasis.

The subtle side to hypoxia inducible factor (HIFalpha) regulation.

The transcription factor hypoxia inducible factor alpha-subunit (HIFalpha) is pivotal in the cellular response to the stress of hypoxia. Post-translational modification of HIFalpha by hydroxylase enzymes has recently been identified as a key "oxygen sensing" mechanism within the cell. The absence of the substrate oxygen prevents the hydroxylases from modifying HIFalpha during hypoxia and allows dramatic up-regulation of both HIFalpha protein stability and transcriptional activation capability.