IOP1, a novel hydrogenase-like protein that modulates hypoxia-inducible factor-1alpha activity.

A central means by which mammalian cells respond to low oxygen tension is through the activation of the transcription factor HIF-1 (hypoxia-inducible factor-1). Under normoxic conditions, HIF-1alpha (the alpha subunit of HIF-1) is targeted for rapid degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, this degradation is inhibited, thereby leading to the stabilization and activation of HIF-1alpha. Here, we report the identification of IOP1 (iron-only hydrogenase-like protein 1), a protein homologous with enzymes present in anaerobic organisms that contain a distinctive iron-sulfur cluster. IOP1 is present in a broad range of cell types. Knockdown of IOP1 using siRNA (small interfering RNA) in mammalian cells increases protein levels of HIF-1alpha under both normoxic and hypoxic conditions, and augments hypoxia-induced HRE (hypoxia response element) reporter gene and endogenous HIF-1alpha target gene expressions. We find that IOP1 knockdown up-regulates HIF-1alpha mRNA levels, thereby providing a mechanism by which knockdown induces the observed effects. The results collectively provide evidence that IOP1 is a component of the protein network that regulates HIF-1alpha in mammalian cells.

Taking aim at fall injury adverse events: best practices and organizational change.

Fall injuries represent a huge healthcare, social and financial burden to the Canadian population. In 2004, the McGill University Health Centre (MUHC) was awarded recognition as a National Spotlight Organization for Implementation of the Registered Nurses Association of Ontario Best Practice Guidelines (BPGs). That same year, the author and co-leader of the Best Practice Guideline Program began the CHSRF Executive Training in Research Application (EXTRA) Program with the goal of reducing falls injuries, one of the most common adverse events in the MUHC and in acute care in Canada. This demonstration project used multiple strategies to strengthen a culture of safety and improve performance relating to adverse events, including: pilot testing several evidence-based falls prevention interventions (autumn 2005), training teams of champions to work across multiple sites, developing an infrastructure to support organizational change, modifying existing quality indicators to become benchmarkable, conducting a cost analysis of falls prevention, evaluating pre- and post-pilot surveys of organizational climate and obtaining initial baseline measures of the safety climate within the organization. Positive patient, practitioner and organizational outcomes suggest that falls safety prevention is feasible in large, complex healthcare organizations--and that safety is both a moral and a financial imperative. Next stages of the BPG program include full rollout, and measuring sustainability via a formal outcome evaluation study.

Practice makes perfect: preparing graduate nurses for professional licensure.

In the fall of 2000, the licensing examination for nursing taken by candidates in the Province of Quebec was altered to include an oral practical component. This article describes how a group of nurse clinician educators, despite severe time and human resources constraints, developed a unique and interactive program to assist graduate unlicensed nurses to successfully prepare for this new examination process.

A ministry of memory: spiritual care for the older adult with dementia.

The primary focus of research related to spiritual and ministry needs of older people, historically and in the present, has been on those whose cognitive abilities are only minimally impaired. The older adult with a dementia like Alzheimer's disease, however, has not received as much attention. This may be related to a lack of any theoretical framework from which to understand what may be happening to a markedly confused person spiritually, and how a person with progressive cognitive impairment might still be able to maintain a relationship with God and be ministered to by a God who may only be remembered vaguely, if at all. Elderly persons with dementia with a faith background rooted in the Judeo-Christian worldview are often able to respond to various rituals of their faith, verbally, physically, and emotionally. Common practices like familiar prayers, Bible readings, hymns, and attendance at worship services where collective memory is shared can serve as memory joggers to reconnect the person, not only to the faith community, but to a faithful God. A spiritual care ministry to older people with dementia can be considered a ministry of memory.

A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation.

BACKGROUND: The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE). RESULTS: Patients with IE were screened for changes in the HIF-1alpha coding sequence, and a change in the ODD domain that converts Pro-582 to Ser was identified in several patients. This same change, however, was also detected at a significant frequency, 0.073, in unaffected controls compared to 0.109 in the IE patient group. In vitro hydroxylation assays examining this amino acid change failed to reveal a discernible effect on HIF hydroxylation at Pro-564. CONCLUSION: The Pro582Ser change represents a common polymorphism of HIF-1alpha that does not impair HIF-1alpha prolyl hydroxylation. Although the Pro582Ser polymorphism is located in the ODD domain of HIF-1alpha it does not diminish the association of HIF-1alpha with VHL. Thus, it is unlikely that this polymorphism accounts for the erythrocytosis in the group of IE patients studied.