Novel characteristics of the biological properties of the yeast Saccharomyces cerevisiae eukaryotic initiation factor 2A

Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G(2)/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of approximately 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.

Human intervertebral disc aggrecan inhibits nerve growth in vitro

OBJECTIVE: To assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques. METHODS: Aggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH-SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared. RESULTS: Disc aggrecan inhibited the growth of neurites from SH-SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration-dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects. CONCLUSION: Nerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.

Precompetitive data sharing as a catalyst to address unmet needs in Parkinson's disease

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease.

Factors associated with social work student satisfaction with field placements in child welfare

This study was conducted during the 1994-1995 academic year. Seven social work education programs in the state of Florida, all accredited by the Council on Social Work Education, participated in this study. Graduate and undergraduate social work students in child welfare field placements, and their field instructors, were surveyed during the Spring 1995 semester to assess their satisfaction with field placements in this area and the relationship of this satisfaction to employment interests and field placement recommendations.^ The majority of social work students responding to this survey were generally satisfied with several aspects of their field placements--the learning, field work program, field instructor, child welfare agency, and overall field experience. The field instructors were generally more satisfied than the students, but only statistically different from the students in the areas of satisfaction with the field work program and the child welfare agency. Multiple regression analysis revealed that learning assignment opportunities, field instructor relationship characteristics, placement preference, and pre-placement interview contributed to the prediction of student satisfaction.^ Student satisfaction in field placement was significantly related to the acceptance of employment, if offered, and the recommendation of the field placement to other students. Logistic regression analysis revealed that satisfaction with the child welfare agency was the greatest contributor to the prediction of acceptance of employment, and satisfaction with the field work program was the greatest contributor to the prediction of field placement recommendation. ^

The use of presidential executive orders to control the management and administration of the federal government

As long as governmental institutions have existed, efforts have been undertaken to reform them. This research examines a particular strategy, coercive controls, exercised through a particular instrument, executive orders, by a singular reformer, the president of the United States. The presidents studied-- Johnson, Nixon, Ford, Carter, Reagan, Bush, and Clinton--are those whose campaigns for office were characterized to varying degrees as against Washington bureaucracy and for executive reform. Executive order issuance is assessed through an examination of key factors for each president including political party affiliation, levels of political capital, and legislative experience. A classification typology is used to identify the topical dimensions and levels of coerciveness. The portrayal of the federal government is analyzed through examination of public, media, and presidential attention. The results show that executive orders are significant management tools for the president. Executive orders also represent an important component of the transition plans for incoming administrations. The findings indicate that overall, while executive orders have not increased in the aggregate, they are more intrusive and significant. When the factors of political party affiliation, political capital, and legislative experience are examined, it reveals a strong relationship between executive orders and previous executive experience, specifically presidents who served as a state governor prior to winning national election as president. Presidents Carter, Reagan, and Clinton (all former governors) have the highest percent of executive orders focusing on the federal bureaucracy. Additionally, the highest percent of forceful orders were issued by former governors (41.0%) as compared to their presidential counterparts who have not served as governors (19.9%). Secondly, political party affiliation is an important, but not significant, predictor for the use of executive orders. Thirdly, management strategies that provide the president with the greatest level of autonomy--executive orders--redefine the concept of presidential power and autonomous action. Interviews of elite government officials and political observers support the idea that executive orders can provide the president with a successful management strategy, requiring less expenditure of political resources, less risk to political capital, and a way of achieving objectives without depending on an unresponsive Congress. ^

Characteristics of effective clinical and theory instructors as perceived by LPN to RN versus generic students in an associate degree nursing program

The purpose of this study was to compare the characteristics of effective clinical and theory instructors as perceived by LPN/RN versus generic students in an associate degree nursing program.^ Data were collected from 508 students during the 1996-7 academic year from three NLN accredited associate degree nursing programs. The researcher developed instrument consisted of three parts: (a) Whitehead Characteristics of Effective Clinical Instructor Rating Scale, (b) Whitehead Characteristics of Effective Theory Instructor Rating Scale, and (c) Demographic Data Sheet. The items were listed under five major categories identified in the review of the literature: (a) interpersonal relationships, (b) personality traits, (c) teaching practices, (d) knowledge and experience, and (e) evaluation procedures. The instrument was administered to LPN/RN students in their first semester and to generic students in the third semester of an associate degree nursing program.^ Data was analyzed using a one factor mutivariate analysis of variance (MANOVA). Further t tests were carried out to explore for possible differences between type of student and by group. Crosstabulations of the demographic data were analyzed.^ There were no significant differences found between the LPN/RN versus generic students on their perceptions of either effective theory or effective clinical instructor characteristics. There were significant differences between groups on several of the individual items. There was no significant interaction between group and ethnicity or group and age on the five major categories for either of the two instruments. There was a significant main effect of ethnicity on several of the individual items.^ The differences between the means and standard deviations on both instruments were small, suggesting that all of the characteristics listed for effective theory and clinical instructors were important to both groups of students. Effective teaching behaviors, as indicated on the survey instruments, should be taught to students in graduate teacher education programs. These behaviors should also be discussed by faculty coordinators supervising adjunct faculty. Nursing educators in associate degree nursing programs should understand theories of adult learning and implement instructional strategies to enhance minority student success. ^

Molecular markers and human history: A tale of two haplogroup systems

To chronicle demographic movement across African Asian corridors, a variety of molecular (sequence analysis, restriction mapping and denaturing high performance liquid chromatography etc.) and statistical (correspondence analysis, AMOVA, calculation of diversity indices and phylogenetic inference, etc.) techniques were employed to assess the phylogeographic patterns of mtDNA control region and Y chromosomal variation among 14 sub-Saharan, North African and Middle Eastern populations. The patterns of genetic diversity revealed evidence of multiple migrations across several African Asian passageways as well within the African continent itself. The two-part analysis uncovered several interesting results which include the following: (1) a north (Egypt and Middle East Asia) to south (sub-Saharan Africa) partitioning of both mtDNA and Y chromosomal haplogroup diversity, (2) a genetic diversity gradient in sub-Saharan Africa from east to west, (3) evidence in favor of the Levantine Corridor over the Horn of Africa as the major genetic conduit since the Last Glacial Maximum, (4) a substantially higher mtDNA versus Y chromosomal sub-Saharan component in the Middle East collections, (5) a higher representation of East versus West African mtDNA haplotypes in the Arabian Peninsula populations versus no such bias in the Levant groups and lastly, (6) genetic remnants of the Bantu demographic expansion in sub-Saharan Africa. ^

A search for an exotic meson in the gamma + P decaying to delta++ + pi- + eta reaction

A Partial Waves Analysis (PWA) of γp → Δ ++X → pπ+ π - (η) data taken with the CLAS detector at Jefferson Lab is presented in this work. This reaction is of interest because the Δ++ restricts the isospin of the possible X states, leaving the PWA with a smaller combination of partial waves, making it ideal to look for exotic mesons. It was proposed by Isgur and Paton that photoproduction is a plausible source for the Jpc=1–+ state through flux tube excitation. The π1(1400) is such a state that has been produced with the use of hadron production but it has yet to be seen in photoproduction. A mass independent amplitude analysis of this channel was performed, followed by a mass dependent fit to extract the resonance parameters. The procedure used an event-based maximum likelihood method to maintain all correlations in the kinematics. The intensity and phase motion is mapped out for the contributing signals without requiring assumptions about the underlying processes. The strength of the PWA is in the analysis of the phase motion, which for resonance behavior is well defined. In the data presented, the ηπ– invariant mass spectrum shows contributions from the a0(980) and a2(1320) partial waves. No π1 was observed under a clear a2 signal after the angular distributions of the decay products were analyzed using an amplitude analysis. In addition, this dissertation discusses trends in the data, along with the implemented techniques.

The market value implications of pension asset allocation

Pension funds have been part of the private sector since the 1850's. Defined Benefit pension plans [DB], where a company promises to make regular contributions to investment accounts held for participating employees in order to pay a promised lifelong annuity, are significant capital markets participants, amounting to 2.3 trillion dollars in 2010 (Federal Reserve Board, 2013). In 2006, Statement of Financial Accounting Standards No.158 (SFAS 158), Employers' Accounting for Defined Benefit Pension and Other Postemployment Plans, shifted information concerning funding status and pension asset/liability composition from disclosure in the footnotes to recognition in the financial statements. I add to the literature by being the first to examine the effect of recent pension reform during the financial crisis of 2008-09. This dissertation is comprised of three related essays. In my first essay, I investigate whether investors assign different pricing multiples to the various classes of pension assets when valuing firms. The pricing multiples on all classes of assets are significantly different from each other, but only investments in bonds and equities were value-relevant during the recent financial crisis. Consistent with investors viewing pension liabilities as liabilities of the firm, the pricing multiples on pension liabilities are significantly larger than those on non-pension liabilities. The only pension costs significantly associated with firm value are actual rate of return and interest expense. In my second essay, I investigate the role of accruals in predicting future cash flows, extending the Barth et al. (2001a) model of the accrual process. Using market value of equity as a proxy for cash flows, the results of this study suggest that aggregate accounting amounts mask how the components of earnings affect investors' ability to predict future cash flows. Disaggregating pension earnings components and accruals results in an increase in predictive power. During the 2008-2009 financial crisis, however, investors placed a greater (and negative) weight on the incremental information contained in the individual components of accruals. The inferences are robust to alternative specifications of accruals. Finally, in my third essay I investigate how investors view under-funded plans. On average, investors: view deficits arising from under-funded plans as belonging to the firm; reward firms with fully or over-funded pension plans; and encourage those funds with unfunded pension plans to become funded. Investors also encourage conservative pension asset allocations to mitigate firm risk, and smaller firms are perceived as being better able to handle the risk associated with underfunded plans. During the financial crisis of 2008-2009 underfunded status had a lower negative association with market value. In all three models, there are significant differences in pre- and post- SFAS 158 periods. These results are robust to various scenarios of the timing of the financial crisis and an alternative measure of funding.

Ecological Homogenization of Urban USA

A visually apparent but scientifically untested outcome of land-use change is homogenization across urban areas, where neighborhoods in different parts of the country have similar patterns of roads, residential lots, commercial areas, and aquatic features. We hypothesize that this homogenization extends to ecological structure and also to ecosystem functions such as carbon dynamics and microclimate, with continental-scale implications. Further, we suggest that understanding urban homogenization will provide the basis for understanding the impacts of urban land-use change from local to continental scales. Here, we show how multi-scale, multi-disciplinary datasets from six metropolitan areas that cover the major climatic regions of the US (Phoenix, AZ; Miami, FL; Baltimore, MD; Boston, MA; Minneapolis–St Paul, MN; and Los Angeles, CA) can be used to determine how household and neighborhood characteristics correlate with land-management practices, land-cover composition, and landscape structure and ecosystem functions at local, regional, and continental scales.