ABSTRACT
Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease resulting from loss of Purkinje neurones within the cerebellum. The ubiquitin proteasome pathway (UPP) has been implicated in SCA1 but the role of proteolysis in the disease is still poorly understood. To further investigate this issue in vivo, genetic crosses were performed between an established mouse model of SCA1 and novel strains expressing elevated levels of wild type or mutant isoforms of ubiquitin. The K48R mutant isoform of ubiquitin (a dominant negative inhibitor of proteolysis) was found to significantly delay the deterioration of Purkinje neurones as evidenced by behavioural, morphological, and molecular indicators. This delay was accompanied by stabilization of p300/CBP, transcriptional mediators whose abundance and activity would otherwise decline in the course of the SCA1 disease, and persistence of protein kinase C gamma (PKCgamma), a protein involved in Purkinje cell dendritic development that is mutated in one form of spinocerebellar ataxia. Whereas the stabilization of p300/CBP was found to occur at the post-translational level the modulation of PKCgamma was at the level of transcription. These results are consistent with transcriptional dysregulation as a key mechanism in neurodegeneration through loss of p300/CBP. Further, the results suggest that the UPP is a potentially useful target for the development of novel therapies for the treatment of neurodegenerative disease.
Subject(s)
Purkinje Cells/pathology , Spinocerebellar Ataxias/metabolism , Ubiquitin/genetics , p300-CBP Transcription Factors/metabolism , Animals , Blotting, Northern , Blotting, Western , Disease Models, Animal , Humans , Immunohistochemistry , Mice , Mice, Transgenic , Mutation , Protein Kinase C/metabolism , Purkinje Cells/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Spinocerebellar Ataxias/genetics , Transcription, Genetic , Ubiquitin/metabolismABSTRACT
The K48R mutant ubiquitin can exert profound in vivo protective effects against a variety of insults, including agents of direct clinical relevance. The manipulation of the ubiquitin/proteasome pathway has enormous potential for clinical benefit, and it is not unreasonable to expect that such benefits will include diseases of aging.
Subject(s)
Aging , Mutation , Ubiquitin/genetics , Animals , Body Temperature , Body Weight , Cisplatin/pharmacology , Cysteine Endopeptidases/metabolism , DNA Damage , Mice , Mice, Transgenic , Multienzyme Complexes/metabolism , Proteasome Endopeptidase Complex , Retroviridae/genetics , Time Factors , Ubiquitin/metabolismABSTRACT
The vital links between nursing workforce research and policy are clear. Documented findings on current and projected continued shortages of nurses have lead to new legislation and policies targeted to increase the numbers of qualified nurses and to improve the image of nurses. These initiatives will be effective only if there is concurrent leadership in the practice arena. Research and policy must be linked to practice through initiatives to strengthen leadership, develop new practice models that improve utilization of nurses and patient satisfaction, and strengthen nursing's participation in decision making in healthcare delivery.
Subject(s)
Nurses/supply & distribution , Forecasting , Health Care Reform , Health Policy , Humans , Nursing Staff, Hospital/organization & administration , Personnel Administration, Hospital , United StatesABSTRACT
Learn how you and your staff can implement a proactive four-point plan to reduce medication errors.
Subject(s)
Medication Errors/psychology , Nursing, Supervisory/organization & administration , Quality Assurance, Health Care/organization & administration , Safety Management/methods , Humans , Planning TechniquesABSTRACT
Learn what steps you should take to implement a palliative-care program that capitalizes on your institution's strengths.
Subject(s)
Nursing, Supervisory/organization & administration , Palliative Care/organization & administration , Program Development/methods , HumansABSTRACT
The current model of transepithelial ion movements in the gill of freshwater fish incorporates an apically oriented vacuolar H(+)-ATPase (H(+)V-ATPase; proton pump) that is believed to facilitate both acid excretion and Na(+) uptake. To substantiate this model, we have cloned and sequenced a cDNA encoding the B subunit of the rainbow trout (Oncorhynchus mykiss) H(+)V-ATPase. The cloning of the B subunit enabled an examination by northern analysis of its tissue distribution and expression during external hypercapnia. Degenerate oligonucleotide primers to the B subunit of the H(+)V-ATPase were designed and used in a semi-nested polymerase chain reaction (PCR) to amplify an 810 base pair (bp) product from a trout gill/kidney cDNA library. This PCR product was cloned and sequenced and then used to screen the same cDNA library. The assembled 2262 bp cDNA included an open reading frame coding for a deduced protein of 502 amino acid residues. A BLAST search of the GenBank nucleotide database revealed numerous matches to other vertebrate and invertebrate H(+)V-ATPase B subunits. Protein alignment demonstrated that the trout H(+)V-ATPase B subunit is more than 85 % identical and more than 90 % similar to those in other vertebrate species. An initial analysis of H(+)V-ATPase mRNA tissue distribution revealed significant expression in blood. Although a comparison of perfused tissues (blood removed) with non-perfused tissues demonstrated no obvious contribution of the blood to total tissue H(+)-ATPase mRNA levels, all subsequent experiments were performed using perfused tissues. Levels of H(+)V-ATPase mRNA expression were high in the gill, kidney (anterior or posterior), intestine, heart and spleen, but lower in liver and white muscle. Exposure of the fish to 12 h of external hypercapnia (water P(CO2)=7. 5 mmHg; 1 kPa) was associated with a transient increase (at 2 h) in the levels of H(+)V-ATPase B subunit mRNA in gill and kidney; liver mRNA levels were unaffected. These results are consistent with the hypothesis of an apically localised plasma membrane H(+)V-ATPase in the freshwater trout gill and that the expression of this proton pump is increased during periods of acidosis, at least in part because of an increased steady-state level of H(+)V-ATPase mRNA.
Subject(s)
Proton-Translocating ATPases/genetics , Vacuoles/metabolism , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Cloning, Molecular , DNA Probes , Evolution, Molecular , Molecular Sequence Data , Oncorhynchus mykiss , Organ Specificity , Polymerase Chain Reaction , Proton-Translocating ATPases/metabolism , RNA, Messenger/analysis , Sequence AlignmentABSTRACT
In organizations without nursing departments, nurses must take additional measures to ensure that they and their colleagues meet nursing standards and ensure quality performance.
Subject(s)
Continuity of Patient Care/organization & administration , Nursing Services/organization & administration , Nursing Staff/organization & administration , Patient Care Team/organization & administration , Quality Assurance, Health Care/organization & administration , HumansABSTRACT
Building a new facility requires careful planning based on consumers' needs and desires.
Subject(s)
Health Facility Moving/organization & administration , Hospital Design and Construction/standards , Nursing, Supervisory/organization & administration , Humans , Planning TechniquesABSTRACT
Changes in both the business and technology of health care place increasing accountability on nurses.
Subject(s)
Nursing Staff/standards , Outcome Assessment, Health Care , Professional Competence , Evidence-Based Medicine , HumansABSTRACT
Read about how to balance RN responsibilities when facilities assign medication administration to Doctors of Pharmacy (PharmDs).
Subject(s)
Medication Systems, Hospital/organization & administration , Pharmacy Service, Hospital/organization & administration , HumansABSTRACT
Three nurse executives offer ways to track short-stay patients for more accurate staff planning.
Subject(s)
Bed Occupancy , Nursing Staff, Hospital/supply & distribution , Nursing, Supervisory/organization & administration , Personnel Staffing and Scheduling/organization & administration , HumansABSTRACT
Here, two nurse executives explain how to involve community members in care management.
Subject(s)
Community Participation , Hospitals, Community , Nurse Administrators , HumansABSTRACT
Here, two nurse executives explain how to work with administrators and physicians to implement a case management program.
Subject(s)
Case Management/organization & administration , Hospital Units/organization & administration , Nursing, Supervisory/organization & administration , Humans , Medical Staff, Hospital , Program DevelopmentABSTRACT
Nurse leaders reduce overtime and use of supplementary staff by establishing resource pools, allocating staff based on nursing hours instead of full-time equivalents, and more.
Subject(s)
Nursing Staff, Hospital/supply & distribution , Personnel Staffing and Scheduling/organization & administration , Workload , Humans , Nursing Staff, Hospital/economics , Nursing, Supervisory/organization & administrationABSTRACT
The American Organization of Nurse Executives (AONE) strives to provide its members with timely and useful information. In this article, the author describes AONE's work to guide the policy process about nurse shortages. The results of this survey will help you practice in your position and in your state, regional, and national policy work. AONE's policy agenda is driven by its mission and commitment to patient care. One of the most current, compelling policy issues is ensuring an adequate supply of nurses to meet the patient care demand. In response to the increasing reports of nurse shortages, AONE engaged the HSM Group, Ltd. to conduct a survey to determine if hospitals were experiencing a shortage. The survey questions were developed with the Health Resources and Services Administration (HRSA), Division of Nursing, the American Nurses Association, and the American Society for Healthcare Human Resources of the American Hospital Association. The Research on Nursing Staff Shortage was published in 1999.
Subject(s)
Nurse Administrators/organization & administration , Nursing Staff, Hospital/supply & distribution , Societies, Nursing/organization & administration , Humans , Nursing Administration Research , Personnel Selection/organization & administration , Surveys and Questionnaires , United StatesABSTRACT
Learn two strategies for reducing medication errors by working collaboratively--and getting back to basics.
