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Selected AbstractsStrain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse StrainsALCOHOLISM, Issue 8 2010Noah R. Gubner Background:, High levels of impulsivity have been associated with a number of substance abuse disorders including alcohol abuse. Research has not yet revealed whether these high levels predate the development of alcohol abuse. Methods:, The current study examined impulsivity in 15 inbred strains of mice (A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57L/J, C58/J, CBA/J, DBA/1J, DBA/2J, NZB/B1NJ, PL/J, SJL/J, SWR/J, and 129P3/J) using a Go/No-go task, which was designed to measure a subject's ability to inhibit a behavior. Numerous aspects of response to ethanol and other drugs of abuse have been examined in these strains. Results:, There were significant strain differences in the number of responses made during the No-go signal (false alarms) and the extent to which strains responded differentially during the Go and No-go signals (d,). The rate of responding prior to the cue did not differ among strains, although there was a statistically significant correlation between false alarms and precue responding that was not related to basal activity level. Interstrain correlations suggested that false alarms and rate of responding were associated with strain differences in ethanol-related traits from the published literature. Conclusions:, The results of this study do support a link between innate level of impulsivity and response to ethanol and are consistent with a genetic basis for some measures of behavioral inhibition. [source] Employment Laws and the Public Sector Employer: Lessons to Be Learned from a Review of Lawsuits Filed against Local GovernmentsPUBLIC ADMINISTRATION REVIEW, Issue 1 2009P. Edward French Numerous aspects of the day-to-day operations of local governments are subject to legal scrutiny; public managers and officials must be keenly aware of the legal rights and protections that extend to both citizens and employees of local governments. This research evaluates several areas of concern in the human resource administration of municipal governments with respect to the management of public employees within the protections set forth by the legislative and judicial branches of the federal government. Sample cases filed from 2000 to 2007 against local governments in Tennessee involving Title VII violations, retaliation, hostile work environment, Family and Medical Leave Act violations, and other employee grievances are detailed. The intent of this analysis is to highlight many of the laws and legal principles that relate to municipal human resources management and to provide scholars and practitioners with a brief overview of the liabilities that may arise from the employment relationship between local governments and their employees. [source] RNA-Interference Approach to Study Functions of NADPH,:,Cytochrome P450 Oxidoreductase in Human HepatocytesCHEMISTRY & BIODIVERSITY, Issue 11 2009Diana Abstract Human NADPH,:,cytochrome P450 oxidoreductase (POR) is encoded by a single gene on chromosome 7q11.2. This flavoprotein donates electrons derived from NADPH to a variety of acceptor proteins, including squalene monooxygenase, heme oxygenase, cytochrome b5, and many microsomal cytochromes P450 (CYPs), which are involved in oxidative drug metabolism, steroidogenesis, and other functions. Numerous aspects related to cellular POR expression have not been systematically investigated. Interestingly, POR expression is lower compared to CYPs and may thus be limiting for monooxygenase activities, but conversely, POR knock-out in mice resulted in compensatory upregulation of CYPs. POR may also influence intracellular cholesterol and lipid homeostasis. To systematically investigate such effects, we developed specific POR gene silencing in cell lines and primary human hepatocytes by RNA interference using small interfering RNAs (siRNAs). In HepG2 cells, POR mRNA could be reduced by 95% over 4 days accompanied by reduced protein content and activity. In primary human hepatocytes, POR mRNA knock-down was less effective and more variable. Analysis of CYPs indicated induction of CYP3A4 but not CYP1A2 or CYP2D6. These results demonstrate that POR can be efficiently and almost completely silenced in HepG2 cells and, at least partially, in primary human hepatocytes. This will allow systematic studies of various consequences of POR variability in human cells. [source] Psychiatric Comorbidity in Epilepsy: A Population-Based AnalysisEPILEPSIA, Issue 12 2007Jose F. Tellez-Zenteno Summary Purpose: The estimated prevalence of mental health disorders in those with epilepsy in the general population varies owing to differences in study methods and heterogeneity of epilepsy syndromes. We assessed the population-based prevalence of various psychiatric conditions associated with epilepsy using a large Canadian national population health survey. Methods: The Canadian Community Health Survey (CCHS 1.2) was used to explore numerous aspects of mental health in persons with epilepsy in the community compared with those without epilepsy. The CCHS includes administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Age-specific prevalence of mental health conditions in epilepsy was assessed using logistic regression. Results: The prevalence of epilepsy was 0.6%. Individuals with epilepsy were more likely than individuals without epilepsy to report lifetime anxiety disorders or suicidal thoughts with odds ratio of 2.4 (95% CI = 1.5,3.8) and 2.2 (1.4,3.3), respectively. In the crude analysis, the odds of lifetime major depression or panic disorder/agoraphobia were not greater in those with epilepsy than those without epilepsy, but the association with lifetime major depression became significant after adjustment for covariates. Conclusions: In the community, epilepsy is associated with an increased prevalence of mental health disorders compared with the general population. Epilepsy is also associated with a higher prevalence of suicidal ideation. Understanding the psychiatric correlates of epilepsy is important to adequately manage this patient population. [source] Inducible gene expression with the Tet-on system in CD4+ T cells and thymocytes of miceGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 7 2007Jisen Huai Abstract CD4+ T cells with their growing list of effector and regulatory subpopulations have vital functions within the immunohematopoietic system. We report here on the first mouse lines that allow temporally and quantitatively controlled expression of transgenes specifically in CD4+ thymocytes and T cells. These were constructed using the Tet-on system. The rtTA2S -M2 version of the reverse tetracycline-dependent transactivator was placed under control of all known CD4 regulatory elements. Reporter transgene expression in mice expressing these constructs is highly specific for CD4+ cells, is strictly dependent on the tetracycline derivative doxycycline, and can be regulated by up to five logs depending on the doxycycline concentration. Moreover, we demonstrate that these mice can be used for noninvasive in vivo imaging of a coexpressed luciferase reporter. These new mouse lines should be highly valuable for studying and manipulating numerous aspects of CD4+ T cell development, biology, and function. genesis 45:427,431, 2007. © 2007 Wiley-Liss, Inc. [source] Exploring the relationship between nursing protocols and nursing practice in an Irish intensive care unitINTERNATIONAL JOURNAL OF NURSING PRACTICE, Issue 4 2005Angela V Flynn RGN BSc(Hons) PGDip(Ed) MSc Nursing practice no longer relies on tradition or ritual; instead, it is based on research and empirical evidence. The emphasis on evidence-based nursing, as well as standardization of nursing practice, has resulted in the production of policies, protocols and guidelines aimed at directing numerous aspects of nursing care. The aim of this study was to explore the relationship between these documents and actual nursing practice. To this end, this descriptive study employed a case study approach to examine the experiences of nurses in an Irish intensive care unit with a protocol on endotracheal tube suctioning. Focus group interviews of 17 nurses in six focus groups provided a significant insight into the experiences of these nurses in relation to policies, protocols and guidelines. Analysis of the data afforded some highly relevant findings, including the fact that nurses adapt clinical protocols as they see fit, thus demonstrating the importance that they place on their own professional judgement and autonomy. [source] ,-Catenin signaling in biological control and cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2007Nancy Gavert Abstract A coordinated integration of cell,cell adhesion and the control of gene expression is essential for the development of multicellular, differentiated organisms. ,-Catenin fulfils important regulatory functions in both cell,cell adhesion by linking cadherin adhesion receptors to the cytoskeleton, and also as a key element in the Wnt signaling pathway where it acts as cotranscriptional activator of target genes in the cell nucleus. Wnt signaling is involved in numerous aspects of embryonic development and in the control of tissue self-renewal in a variety of adult tissues. Hyperactivation of Wnt signaling, mostly by affecting ,-catenin functions, is a hallmark of colon cancer and of many other human cancers. In this prospect, we discuss studies pointing to the molecular mechanisms that govern the integration between cell,cell adhesion and gene expression, as reflected in the switches between these two functions of ,-catenin in colon cancer cells. J. Cell. Biochem. 102: 820,828, 2007. © 2007 Wiley-Liss, Inc. [source] Pediatric lung disease: From proteinases to pulmonary fibrosisPEDIATRIC PULMONOLOGY, Issue 5 2005Felix Chua MRCP Abstract One distinctive outcome of interstitial lung diseases in childhood is the abnormal accumulation of pulmonary extracellular matrix. The clinical consequence of such excessive connective tissue accumulation is known as pulmonary fibrosis. While numerous aspects of its pathogenesis have become familiar, many key events involved in its inception and progression still remain unclear. There is now compelling evidence that lung damage due to uncontrolled proteolysis may help drive critical processes that regulate fibrotic matrix remodeling. In this regard, a number of proteinases have been implicated in promoting both the initial lung injury and the fibroproliferative repair that follows. This review summarizes the knowledge of how different matrix-targeting enzymes may act to influence the development of pediatric pulmonary fibrosis. Understanding the scientific basis of this complex process may highlight opportunities to limit unwanted proteolysis and the intensity of its fibrotic sequelae. © 2005 Wiley-Liss, Inc. [source] Developmental origins of disruptive behaviour problems: the ,original sin' hypothesis, epigenetics and their consequences for preventionTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 4 2010Richard E. Tremblay This paper reviews publications on developmental trajectories of disruptive behaviour (DB) problems (aggression, opposition-defiance, rule breaking, and stealing-vandalism) over the past decade. Prior to these studies two theoretical models had strongly influenced research on DB: social learning and disease onset. According to these developmental perspectives, children learn DB from their environment and onset of the disease is triggered by accumulated exposition to disruptive models in the environment, including the media. Most of the evidence came from studies of school age children and adolescents. Longitudinal studies tracing developmental trajectories of DB from early childhood onwards suggest an inversed developmental process. DB are universal during early childhood. With age, children learn socially acceptable behaviours from interactions with their environment. A ,disease' status is given to children who fail to learn the socially acceptable behaviours. The mechanisms that lead to deficits in using socially accepted behaviours are strongly intergenerational, based on complex genetic and environmental contributions, including epigenetic mechanisms. Prevention of these deficits requires early, intensive and long-term support to parents and child. Newly discovered epigenetic mechanisms suggest that intensive perinatal interventions will have impacts on numerous aspects of physical and mental health, including DB. This review also concludes that: a) subtypes of disruptive behaviours should not be aggregated because they have different developmental trajectories and require specific corrective interventions; b) the overt,covert and destructive,nondestructive dimensions appear the most useful to create DB subtypes; c) overt DB onset before covert DB because the latter require more brain maturation; d) DB subtype taxonomies are more useful for clinicians than developmental taxonomies because the latter are post mortem diagnoses and clinicians' retrospective information is unreliable; e) we need large-scale collaborative preventive experimental interventions starting during early pregnancy to advance knowledge on causes and prevention of DB problems. [source] CYP707A3, a major ABA 8,-hydroxylase involved in dehydration and rehydration response in Arabidopsis thalianaTHE PLANT JOURNAL, Issue 2 2006Taishi Umezawa Summary Abscisic acid (ABA) catabolism is one of the determinants of endogenous ABA levels affecting numerous aspects of plant growth and abiotic stress responses. The major ABA catabolic pathway is triggered by ABA 8,-hydroxylation catalysed by the cytochrome P450 CYP707A family. Among four members of Arabidopsis CYP707As, the expression of CYP707A3 was most highly induced in response to both dehydration and subsequent rehydration. A T-DNA insertional cyp707a3-1 mutant contained higher ABA levels in turgid plants, which showed a reduced transpiration rate and hypersensitivity to exogenous ABA during early seedling growth. On dehydration, the cyp707a3-1 mutant accumulated a higher amount of stress-induced ABA than the wild type, an event that occurred relatively later and was coincident with slow drought induction of CYP707A3. The cyp707a3 mutant plants exhibited both exaggerated ABA-inducible gene expression and enhanced drought tolerance. Conversely, constitutive expression of CYP707A3 relieved growth retardation by ABA, increased transpiration, and a reduction of endogenous ABA in both turgid and dehydrated plants. Taken together, our results indicate that CYP707A3 plays an important role in determining threshold levels of ABA during dehydration and after rehydration. [source] Molecular and morphological supertree of stony corals (Anthozoa: Scleractinia) using matrix representation parsimonyBIOLOGICAL REVIEWS, Issue 4 2005Alexander M. Kerr ABSTRACT The supertree algorithm matrix representation with parsimony was used to combine existing hypotheses of coral relationships and provide the most comprehensive species-level estimate of scleractinian phylogeny, comprised of 353 species (27% of extant species), 141 genera (63%) and 23 families (92%) from all seven suborders. The resulting supertree offers a guide for future studies in coral systematics by highlighting regions of concordance and conflict in existing source phylogenies. It should also prove useful in formal comparative studies of character evolution. Phylogenetic effort within Scleractinia has been taxonomically uneven, with a third of studies focussing on the Acroporidae or its most diverse genera. Sampling has also been geographically non-uniform, as tropical, reef-forming taxa have been considered twice as often as non-reef species. The supertree indicated that source trees concur on numerous aspects of coral relationships, such as the division between robust versus complex corals and the distant relationship between families in Archaeocoeniina. The supertree also supported the existence of a large, taxonomically diverse and monophyletic group of corals with many Atlantic representatives having exsert corallites. Another large, unanticipated clade consisted entirely of solitary deep-water species from three families. Important areas of ambiguity include the relationship of Astrocoeniidae to Pocilloporidae and the relative positions of several, mostly deep-water genera of Caryophylliidae. Conservative grafting of species at the base of congeneric groups with uncontroversial monophyletic status resulted in a more comprehensive, though less resolved tree of 1016 taxa. [source] SUMOylation and cell signallingBIOTECHNOLOGY JOURNAL, Issue 12 2009Artemisia M. Andreou Abstract SUMOylation is a highly transient post-translational protein modification. Attachment of SUMO to target proteins occurs via a number of specific activating and ligating enzymes that form the SUMO-substrate complex, and other SUMO-specific proteases that cleave the covalent bond, thus leaving both SUMO and target protein free for the next round of modification. SUMO modification has major effects on numerous aspects of substrate function, including subcellular localisation, regulation of their target genes, and interactions with other molecules. The modified SUMO-protein complex is a very transient state, and it thus facilitates rapid response and actions by the cell, when needed. Like phosphorylation, acetylation and ubiquitination, SUMOylation has been associated with a number of cellular processes. In addition to its nuclear role, important sides of mitochondrial activity, stress response signalling and the decision of cells to undergo senescence or apoptosis, have now been shown to involve the SUMO pathway. With ever increasing numbers of reports linking SUMO to human disease, like neurodegeneration and cancer metastasis, it is highly likely that novel and equally important functions of components of the SUMOylation process in cell signalling pathways will be elucidated in the near future. [source] Knowledge Translation in International Emergency Medical CareACADEMIC EMERGENCY MEDICINE, Issue 11 2007L. Kristian Arnold MD More than 90% of the world population receives emergency medical care from different types of practitioners with little or no specific training in the field and with variable guidance and oversight. Emergency medical care is being recognized by actively practicing physicians around the world as an increasingly important domain in the overall health services package for a community. The know-do gap is well recognized as a major impediment to high-quality health care in much of the world. Knowledge translation principles for application in this highly varied young domain will require investigation of numerous aspects of the knowledge synthesis, exchange, and application domains in order to bring the greatest benefit of both explicit and tacit knowledge to increasing numbers of the world's population. This article reviews some of the issues particular to knowledge development and transfer in the international domain. The authors present a set of research proposals developed from a several-month online discussion among practitioners and teachers of emergency medical care in 16 countries from around the globe and from all economic strata, aimed at improving the flow of knowledge from developers and repositories of knowledge to the front lines of clinical care. [source] |