Induction of NF-κB by the Akt/PKB kinase

AbstractThe serine/threonine kinase Akt (also known as protein kinase B, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase. Akt can couple to pathways that regulate glucose metabolism or cell survival [1]. Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16 [2–4]. Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-κB family of transcription factors in the Jurkat T-cell line. This induction occurs, at least in part, at the level of degradation of the NF-κB inhibitor IκB, and is specific for NF-κB, as other inducible transcription factors are not affected by Akt overexpression. Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt. Also, Akt does not act alone to induce cytokine promoters and NF-κB reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-κB induction that could have implications for the control of T-cell growth and survival

Addressing Psychosocial Care Using an Interactive Web site for Combat‐Wounded Patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98760/1/ppc344.pd

Self-Regulation of Emotion, Functional Impairment, and Comorbidity Among Children With AD/HD

Objective: This study investigated the role of self-regulation of emotion in relation to functional impairment and comorbidity among children with and without AD/HD. Method: A total of 358 probands and their siblings participated in the study, with 74% of the sample participants affected by AD/HD. Parent-rated levels of emotional lability served as a marker for self-regulation of emotion. Results: Nearly half of the children affected by AD/HD displayed significantly elevated levels of emotional lability versus 15% of those without this disorder. Children with AD/HD also displayed significantly higher rates of functional impairment, comorbidity, and treatment service utilization. Emotional lability partially mediated the association between AD/HD status and these outcomes. Conclusion: Findings lent support to the notion that deficits in the self-regulation of emotion are evident in a substantial number of children with AD/HD and that these deficits play an important role in determining functional impairment and comorbidity outcomes

Nurse staffing levels revisited: a consideration of key issues in nurse staffing levels and skill mix research.

AIM: This paper revisits the published evidence relating to how nurse staffing levels impact on patient, nurse and service outcomes and considers the implications of this body of research for nurse managers in their quest to determine optimum nursing numbers. BACKGROUND: Within the context of the recognized global nursing shortage and particular local pressures within international health services, questions of appropriate nurse staffing levels and skill mix are once again becoming increasingly important. It would seem that the determination of optimum nurse staffing levels and skill mix is a central issue in relation to health service governance, service user involvement, as well as in the recruitment, retention and well-being of nursing staff across the service sectors. METHODS: A review of published evidence was carried out, applying key principles of the systematic method, in order to facilitate the identification of current factors and issues in nurse staffing levels research. The review did not seek to address a specific research question. The search covered 10 years from 1998 to 2008 and identified more than 500 relevant papers, giving a wide international perspective. KEY ISSUES: The majority of research in the field relates to the acute service sector and there are considerable similarities in issues that transcend international boundaries. Much of the research focuses on the impact on patients and nurses of 'poor' nurse staffing levels. More recent studies have explored the impact of nurse staffing levels on the service organization itself. However, while there may be an association between models of nurse staffing and outcomes, there is insufficient evidence to establish a causal relationship between these factors. In this context it is perhaps time to reconsider how nursing outcomes are defined and measured. IMPLICATIONS FOR NURSING MANAGEMENT AND CONCLUSION: Nurse managers, commissioners of services and workforce planners need to be cognisant of key issues and analyses in the consideration of nurse staffing levels. Not least of these is the need for a healthy degree of caution regarding the supposed objectivity, scientific basis, or evidence base, for rational calculation of optimum nurse staffing levels

Polyubiquitin binding to ABIN1 is required to prevent autoimmunity

The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO), a component of the inhibitor of NF-kappa B (I kappa B) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88(-/-) mice, demonstrating that toll-like receptor (TLR)-MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-alpha/beta, c-Jun N-terminal kinases, and p38 alpha mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity

Comment Letter to the U.S. Treasury Department Concerning the Regulatory Structure for Financial Institutions

This comment letter was submitted to the U.S. Treasury Department in connection with that Department\u27s review of proposals for changes in the regulatory structure for financial institutions. The comment letter presents the following policy recommendations: (1) the thrift charter should be eliminated, existing thrifts should be required to convert into banks, and the Office of Thrift Supervision should be merged with the Office of the Comptroller of the Currency (OCC); (2) the dual banking system should be preserved and strengthened in order to promote innovation in banking regulation and to support the community bank sector; (3) at least one federal agency that is separate and independent from the OCC should be designated as the primary federal regulator for state-chartered banks; (4) the existing statutory limits on bank mergers and acquisitions should be maintained, including the 10% nationwide deposit cap and the 30% statewide deposit cap; (5) greater scrutiny and special conditions should be required for large bank mergers; (6) Congress should establish federal consumer protection standards for all home mortgage lenders, credit card lenders, and other providers of consumer credit; (7) Congress should prohibit the OCC from issuing regulations that preempt state law, except in specific areas where Congress has given the OCC explicit authority to adopt preemptive rules; (8) Congress should establish a separate and independent federal authority to enforce federal consumer protection laws against all providers of financial services, including national banks; (9) Congress should recognize the authority of state attorneys general to enforce applicable state laws against all financial service providers, including national banks, (10) Congress should provide the Federal Reserve Board (FRB) with direct oversight over all significant financial conglomerates that control FDIC-insured banks; (11) Congress should prohibit the FDIC\u27s deposit insurance fund from making any payments to uninsured depositors or other uninsured claimants; and (12) all responsibility for protecting uninsured creditors of too big to fail (TBTF) financial institutions should be assigned to the FRB, and the FRB should impose assessments on significant financial conglomerates to recover the FRB\u27s cost of providing financial assistance to TBTF institutions

Low Dose Fluphenazine Decanoate in Treatment of Schizophrenia 341 Maintenance

Abstract. T