bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Magnesium-Amiodarone Step-Up Scheme in Critically Ill Patients With New-Onset Atrial Fibrillation: A Prospective Observational Study
Authors: Sleeswijk Mengalvio E. , Tulleken Jaap E. , Van Noord Trudeke , Meertens John H. J. M. , Ligtenberg Jack J. M. , Zijlstra Jan G.
Published: January 2008

Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO 4) has shown to be effective for both rate and rhythm control, to act synergistically with antiarrhythmic drugs, and to prevent proarrhythmia. Treatment with MgSO4 may reduce the need for antiarrhythmic drugs such as amiodarone in critically ill patients with new-onset atrial fibrillation. The efficacy of a new institutional protocol was evaluated. Patients were treated with a new institutional protocol for new-onset atrial fibrillation in critically ill patients. An MgSO4 bolus (0.037 g/kg body weight in 15 minutes) was followed by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given to those not responding to MgSO4 within 1 hour. Clinical response was defined as conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of the 29 patients responded to MgSO4 monotherapy, whereas the addition of amiodarone was needed in 13 patients. Median (range) time until conversion to sinus rhythm after MgSO4 was 2 (1-45) hours. Median (range) conversion time in patients requiring amiodarone was 4 (2-78) hours, and median (range) conversion time in all patients was 3 (1-78) hours. The 24-hour conversion rate was 90%. Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step-up scheme reduces the need for amiodarone, effectively converts new-onset atrial fibrillation into a sinus rhythm within 24 hours, and seems to be safe in critically ill patients.
Questions of Method: Fundamental Problems Reading Dialectical Methodologies
Authors: Paolucci Paul
Published: January 2008

Marx admittedly could have been more helpful in making clear and precise his methodological foundations. Leaving key issues scattered over his works has forced a slow reconstruction of Marxist epistemology by subsequent students. Grasping both the philosophy of internal relations and methods of abstraction allows analysis to interpret Marx's work in four broad, separate but interrelated moments: the dialectical method, historical materialism, political-economics, and the communist political project. Failing to grasp these relations in conjunction with failing to take seriously Marx's commitment to identifiable and accepted scientific methods has resulted in both over-precision and under-precision in reconstruction of his methodology. Subsequent schools of thought have generally made similar errors that can be identified, as can progress over time in the clarification of theoretical and epistemological questions.
Small Business, Status Politics, and the Social Base of New Christian Right Activism
Authors: Burris Val
Published: January 2008

This paper examines the social base of Christian Right activism, using data on approximately 3,000 members and financial supporters of a single state-level Christian Right organization: the Oregon Citizens' Alliance (OCA). The findings of the study are consistent with theories that identify “status anxiety” among marginal or threatened segments of the middle class as a motivation for right-wing activism. The class of small business owners was the most overrepresented group among OCA activists. Members of the salaried middle class were also overrepresented, although to a lesser degree. Contrary to expectations, OCA activism was not disproportionately high among elderly persons or in the most rural areas of the state. The paper also illustrates the prevalence of status concerns in the rhetoric of the OCA's anti-abortion and anti-gay campaigns.
Physician Stipends as Organizational Deviance in for-Profit Psychiatric Hospitals
Authors: Vandenburgh Henry
Published: January 2008

For-profit psychiatric hospitals sometimes pay staff physicians large stipends for ostensible medical directorships. This can indicate organizational deviance, a condition where businesses break community norms. Physicians are typically the source of 60 percent of a hospital's admissions. They are free to hospitalize patients at other facilities if they choose. Hospitals thus find it in their interest to create financial incentives. Most states forbid direct kickbacks for referrals, but stipends are justified by the fact that the physicians perform ostensible duties at a hospital. Here, interviews are used to show how these payments operate in the Texas market. A quantitative section then documents the relationship between payment amounts and referrals. Factors prompting high physician payments are also explored. Stipends continue as an important problem that increases health costs and causes psychiatrists to act in their own as opposed to patient interests.
The Manifesto and the Middle Class
Authors: Dassbach Carl
Published: January 2008

This paper examines Marx's claim in the Manifesto that capitalist society would polarize into two classes in light of the current evidence on growing inequality in American society. It argues that the middle class of industrial society is not an anomaly but a product of the incomplete development of capitalism and this middle class is presently being threatened with extinction through technological innovations in the forces of production.
Apples are the Color of Blood
Authors: Russell Steve
Published: January 2008

Color is such a defi ning characteristic of America's racial disharmony that minorities often huddle together under the sobriquet “people of color.” This essay examines the signifi cance of color to American Indians — the only ethnic minority subjected to a government certifi cation process — and concludes that neither skin color nor a certifi cate of degree of Indian blood from the Bureau of Indian Affairs is suffi cient to defi ne Indian identity. No alternative is suggested that would make Indians identifi able by visual regard.
What Does “Black” Mean? Exploring the Epistemological Stranglehold of Racial Categorization
Authors: Brunsma David L. , Rockquemore Kerry Ann
Published: January 2008

The “check all that apply” approach to race on the 2000 census has ignited a conceptual debate over the meaning and usefulness of racial categories. This debate is most intense over the category “black” because of the historically unique way that blackness has been defined. Though the lived reality of many people of color has changed over the past three decades, we question whether the construct black has mirrored these changes and if “black” remains a valid analytic or discursive unit today. While black racial group membership has historically been defined using the one-drop rule, we test the contemporary salience of this classifi cation norm by examining racial identity construction among multiracial people. We fi nd that that the one-drop rule has lost the power to determine racial identity, while the meaning of black is becoming increasingly multidimensional, varied, and contextually specifi c. Ultimately, we argue that social, cultural and economic changes in post-Civil Rights America necessitate a re-evaluation of the validity of black as social construct and re-assessment of its' continued use in social science research.
Exploring the Racial Discrimination and Competition Processes of Race-Specific Violence in the Urban Context
Authors: Parker Karen F. , Mccall Patricia L. , Lane Jodi
Published: January 2008

There has been increasing effort devoted to examining the linkages between urban disadvantage and race-specifi c violence in the sociological literature. Much of this literature has either focused on identifying the consequences of urban disadvantage on different racial groups, particularly as it relates to offending rates, or documenting the impact of labor market factors on intra-racial and inter-racial violence. While this literature advances our understanding of the interconnections between race, economic disadvantage and violence in the urban context, our exploration into this literature has only begun. In this paper, we outline the contributions of the racial stratifi cation literature to the study of urban violence and argue that this literature plays an essential role in moving the study of race and urban violence forward. We offer ways (avenues) to incorporate the racial competition and exploitation literature into the study of violence within and between racial groups. In doing so, we emphasize the importance of “process” by delineating the interconnections between labor market exploitation, competition, and violence.
Conceptualizing Moral Panic through a Moral Economy of Harm
Authors: Hier Sean P.
Published: January 2008

This paper explicates a critical theory of moral panic, arguing that there is an affinity to be discerned between the sociology of moral panic and the sociology of moral regulation. It is demonstrated how efforts to distance sociological investigations of moral regulation from studies of moral panic have been founded on a narrow treatment of the ways in which the latter have conceptualized panics uncritically as irrational societal overreactions stemming from some variant of `social anxiety.' Advocating a conceptualization which attends to the complexity of ways in which human conduct is governed, explanatory importance is situated in Valverde's formulation of `moral capital,' showing how her model not only enables a fusion between a political economy of the state and ethical subjectivity, but more crucial between panics and regulatory projects through the production of a moral economy of harm.
Local Actors, Nation States, and Their Global Environment: Conceptualizing Successful Resistance to the Anti-Social Impacts of Globalization
Authors: Dujon Veronica
Published: January 2008

Nation-states are faced with multiple contradictions as they mediate the insertion of their domestic economies into the global economy. Drawing on a case study from the Caribbean country of St. Lucia, this paper explores how local community resources may infl uence the terms of their integration in the global economy. It is argued that socially embedded economic institutions that are typically neglected in discussions of economic development are in some ways better suited to the task of infl uencing the terms of globalization than state policy-making.
Beyond the Confines: Management, Colonization and the Everyday
Authors: Hancock Philip , Tyler Melissa
Published: January 2008

Drawing on critical social theory, this article argues that critical management studies (CMS) should extend its analytical gaze beyond the work organization and consider the ways in which management increasingly appears to colonize the subjectivity-constituting experiences and practices of everyday life. This argument is developed with reference to a discussion of various illustrations of the cultural ubiquity of management. The article concludes by reaffirming the need to develop a critical study of management as a social phenomenon, one that broadens the focus of CMS beyond the confines of the business school and its concern with organizational management in order to develop a sustained critique of this managerial colonization of the lifeworld.
Corporate Social Responsibility: The Good, the Bad and the Ugly
Authors: Banerjee Subhabrata Bobby
Published: January 2008

In this article I critically analyze contemporary discourses of corporate social responsibility and related discourses of sustainability and corporate citizenship. I argue that despite their emancipatory rhetoric, discourses of corporate citizenship, social responsibility and sustainability are defined by narrow business interests and serve to curtail interests of external stakeholders. I provide an alternate perspective, one that views discourses of corporate citizenship, corporate social responsibility, and sustainability as ideological movements that are intended to legitimize and consolidate the power of large corporations. I also problematize the popular notion of organizational `stakeholders'. I argue that stakeholder theory of the firm represents a form of stakeholder colonialism that serves to regulate the behavior of stakeholders. I conclude by discussing implications for critical management studies.
The Political Economy of Markets and Development: A Case Study of Health Care Consumption in the State of Kerala, India
Authors: Varman Rohit
Published: January 2008

Marketing theory has largely ignored the issue of power in influencing exchanges. Most of the studies either disregard the role of power, or resource power is the only dimension taken into account. In this study, we expand the existing understanding by centrally situating the role of socio-political power in the consumption process. We examine the health care system in the Indian state of Kerala and highlight that socio-political power is a crucial determinant of consumption levels. In the process, we argue that in a resource—constrained Third World society socio-political empowerment is critical to the development process.
Three Ideologies of Individualism: Toward Assimilating a Theory of Individualisms and their Consequences
Authors: Greene T. William
Published: January 2008

Accompanying capitalism, individualistic beliefs have advanced individual rights and freedoms. Social critics, however, argue that individualism justifies inequalities by suggesting that barriers to economic well being exist only in the psyches of individuals, and not also within social structures. A single ideology of individualism could not effectively cross all lines of social difference in the USA. Consequently, supplemental ideologies emphasizing full self-reliance and high self-esteem emerged at historically important junctures, reaching diverse populations and circumventing structural strain. Separated or intertwined, these ideologies may contribute to negative social consequences. Americans are described as simultaneously `too individualistic' and `not individualistic enough.'
The Goals of the Foundation of Ethnic Minority Non-Governmental Organizations in Latvia
Authors: Racko Girts
Published: January 2008

The transition to liberal democracy and market economy in Latvia after the breakdown of the Soviet regime was related to an increase in ethnic minority non-governmental organizations (NGOs). Drawing on the results of in-depth interviews with leaders and the analysis of the statutes of ethnic minority NGOs, the study presented here compares the goals of the foundation of ethnic minority NGOs in 1993 and 2003 in relation to historical opportunity structures that have made their institutionalization possible. Following Bourdieu's theory of social reproduction, the study reveals distinctive goal priorities among the older and more recently registered organizations.1
Using Computer Listserves To Achieve a More Diverse Classroom: the “Virtual Salon”
Authors: Steiger Thomas L. , Levine Rhonda F.
Published: January 2008

Two stratification courses, one at an elite private liberal arts college and another at a regional state university were joined through a listserve or computer mailing list . Students were required to participate in the “virtual salon.” The primary goal of the virtual salon was to increase the diversity of students discussing topics common in the courses. The virtual salon was successful in achieving this goal as well as making it a meaningful learning experience by creating passionate engagement in the material, the students shared knowledge, and a sense of community was created where students from diverse backgrounds felt comfortable expressing themselves.
Contribution of TNF and of LPS in endotoxemic shock in mice. A reappraisal
Authors: Heumann Didier , Le Roy Didier , Glauser Michel Pierre
Published: January 2008

Species of mice have a different sensitivity to LPS. The mechanisms underlying these differences are not clear. We have investigated the contribution of TNF and of LPS in inducing lethality in endotoxemic models using LPSsensitive C57BI/6 and Balb/c mice, OF1 mice with an intermediate sensitivity, and LPS-resistant C3H/HeJ mice. Our observations showed that TNF largely contributed to lethality, since anti-TNF antibodies protected sensitive Balb/c mice from death over a large range of LPS concentrations. OF1 mice were relatively insensitive to LPS and this was associated with a lesser production of TNF. Similarly, OF1 mice had a reduced sensitivity to challenge with recombinant TNF than Balb/c mice. These observations, therefore, indicated that TNF production and sensitivity were determinant for outcome upon LPS challenge. LPS levels were similar in Balb/c, C57BI/6, and OF1 mice, suggesting that a difference in LPS clearance did not contribute to the differences in sensitivity to LPS. The contribution of the combination of both TNF and LPS in endotoxemic shock was investigated with the LPS-resistant C3H/HeJ mice. While these mice were resistant to challenge with either LPS or a low dose of TNF, combination of non lethal concentrations of LPS and TNF induced death. These data, thus, suggest that while TNF is critical for mediating LPS-induced death, the combination of both LPS and TNF act synergistically in contributing to death, particularly in animal species with reduced sensitivity to LPS.
The Ethics of Escape: British Officer POWs in the First World War
Authors: MacKenzie S.P.
Published: January 2008

In the absence of official guidance, British officers taken prisoner in the First World War had to decide for themselves whether or not attempts at escape were justified. Their decisions varied according to individual perceptions of duty, but it was those who chose to escape who saw their memoirs published in the interwar years. There was still little official direction concerning behaviour in captivity in the first years of the Second World War, yet officers who found themselves in enemy hands early on could draw on what their Great War counterparts had written about the ethics of escape.
The `Step-by-Step' Approach: British Military Thought and Operational Method on the Western Front, 1915—1917
Authors: Harris Paul , Marble Sanders
Published: January 2008

The British Expeditionary Force of the First World War did not fight a deliberately attritional war, despite the heavy casualties and slow gains it experienced. Before the BEF launched a single trench-warfare attack, senior officers argued for a methodical and clearly attritional operational approach, accepting limited gains and slow overall progress to get a favourable casualty exchange rate. The idea quickly had senior adherents, especially Sir William Robertson. Sir Douglas Haig, however, was consistently optimistic, thinking breakthroughs were possible; this prejudiced him against lesser, attritional, attacks. Not until mid-1917 did the BEF substantially adopt methodical step-by-step attacks.
Mapping the Processes and Qualities of Spiritual Nursing Care
Authors: Carr Tracy
Published: January 2008

Although the importance of spiritual care is widely recognized in nursing theory, recent research suggests that it is rarely attended to in nursing practice. One explanation for this contradiction is the conceptual confusion that exists regarding the meaning of spiritual nursing care. To help unravel this confusion, in-depth open-ended interviews were conducted in an oncology care setting with 29 individuals representing the multiple perspectives of nurses, patients, family, and others. Phenomenological analysis of these interviews reveals that spiritual nursing care involves a complexity of social processes, of which developing caring relationships is core. For these social processes to work and for spiritual nursing care to be realized, the nurse must embody four essential human qualities: receptivity, humanity, competency, and positivity. Participants' descriptions of these processes and qualities not only offer clarity and understanding but also capture the diffuse and amorphous nature of spiritual nursing care.
Workplace Violence, Employer Liability, and Implications for Organizational Research
Authors: Paetzold Ramona L. , O'Leary-Kelly Anne , Griffin Ricky W.
Published: January 2008

Organizations face potential liability whenever workplace violence occurs inside their boundaries. Focusing on violent behaviors between employees, the authors examine the major legal theories that apply most often in workplace violence scenarios—negligence (state law), sexual harassment law (federal law), and the Americans with Disabilities Act (federal law). The purpose is to highlight avenues for organizational research that arise because of the legal issues that employers face. For each source of liability, the authors identify major research questions that should be studied in organizational science, particularly by aggression and violence researchers.
Why Don't More Senior Leaders Mentor?
Authors: Satter Andrew M. , Russ Diane E.
Published: January 2008

Large organizations are facing a pending talent drain when baby boomer generation senior leaders begin retiring over the next 3 to 5 years. As companies scramble to develop and retain their next generation of leaders, many overlook a cost-effective, tried-and-true method for engagement and leadership development—mentoring. According to the authors' 2-year in-depth research study with senior American business leaders across 20 different industries, mentoring engages high potentials, helps develop essential “soft” skills (e.g., “navigating the culture”), and sends the message that they are valued. It is unfortunate that many executives choose not to mentor, and they may, according to the authors, be mortgaging the future of their companies in the process. The authors have identified five of the most common excuses cited by senior executives who choose not to mentor (e.g., “It doesn't work”) and offer specific strategies to overcome the resistance that senior leaders have about mentoring.
On-Site or Out-of-Sight?
Authors: Hoobler Jenny M.
Published: January 2008

“Family-friendly” initiatives are gaining in popularity as employers attempt to ease the fit between work and family. A number of organizations offer on- or near-site child care facilities to employees with young children. The author uses social identity theory to make the argument that family-friendly policies blurring the lines between work roles and family/caregiver roles serve to reinforce gender biases that degrade women's status on the job. Because women are the primary users of on-site child care services, and family roles are devalued in managerial employment, such “family-friendly” programs force women to sacrifice the quest for workplace equality, opting instead for short-term solutions.
Nurse Aide Agency Staffing and Quality of Care in Nursing Homes
Authors: Castle Nicholas G. , Engberg John , Aiju Men
Published: January 2008

Data from a large sample of nursing homes are used to examine the association between use of nurse aide agency staff and quality. Agency use data come from a survey conducted in 2005 ( N = 2,840), and the quality indicators come from the Nursing Home Compare Web site. The authors found a nonlinear relationship between nurse aide agency levels and quality; however, in general, higher nurse aide agency levels were associated with low quality. The results have policy and practice implications, the most significant of which is that use of nurse aide agency staff of less than 14 full-time equivalents per 100 beds has little influence on quality, whereas nurse aide agency staff of more than 25 full-time equivalents per 100 beds has a substantial influence on quality.
The Response of Small Businesses to Variation in the Price of Health Insurance
Authors: Kronick Richard , Olsen Louis C. , Gilmer Todd P.
Published: January 2008

There is substantial interest in attempts to reduce the number of uninsured persons by providing subsidies to small businesses. To measure the responsiveness of small businesses to offers of subsidized coverage, the authors conducted a randomized controlled trial in which selected groups of San Diego businesses were offered the opportunity to purchase coverage at prices ranging from $20 to $100 per month for an employee-only policy. At $20 per month, an estimated 40% of eligible businesses purchased insurance; at $100 per month, 13% purchased insurance. Small businesses not currently offering insurance to employees are not very responsive to large reductions in the price of coverage. Programs to subsidize insurance for small businesses and their employees are unlikely to substantially reduce the number of uninsured persons.
Sense of Differentness in the Construction of Knowledge
Authors: Enosh Guy , Ben-Ari Adital , Buchbinder Eli
Published: January 2008

This article contributes to the body of knowledge on qualitative interviewing in as much as it highlights the inherent connection between a sense of differentness among interview partners and processes of knowledge construction, which is the overarching goal of qualitative research. The authors argue that a sense of differentness serves as the starting point for the production of knowledge through exploration and reflection, conflict, negotiation, and argumentation. For heuristic purposes, the authors organize the analysis around four conceptual alternatives regarding agreement or disagreement with respect to the moral stances of interview partners. The authors then examine each of the alternatives in terms of its implications for the knowledge construction process and discuss them with regard to ontological, epistemological, and moral levels of analysis.
A Multiple-Perspective Approach to Data Analysis in Congruence Research
Authors: Cheung Gordon W.
Published: January 2008

Despite the popularity of the congruence construct (similarity, fit, and agreement) in organizational theories, the operationalization of congruence and the appropriate methods to analyze it have concerned many researchers. A structural equation modeling-based latent congruence model (LCM) that operationalizes congruence as the mean and difference of the component measures has recently been introduced. The LCM provides a simple analytical framework for examining the measurement equivalence of the component measures and for conducting congruence analysis and component analysis. The objective of this note is to highlight the similarities and differences between the LCM and the polynomial regression (PR) approach to studying congruence. The major difference is that the LCM considers congruence and its components as distinctive constructs, and therefore they can be used to answer different research questions. The determination of which constructs and analytical approach to use should be based on the theory and research hypotheses that answer the research question. Indeed, because LCM provides a simple framework for both congruence analysis and component analysis, researchers are encouraged to answer their research questions from both perspectives.
Requirement of c-Myb for p210BCR/ABL-dependent transformation of hematopoietic progenitors and leukemogenesis
Authors: Lidonnici Maria Rosa , Corradini Francesca , Waldron Todd , Bender Timothy P. , Calabretta Bruno
Published: January 2008

The c-Myb gene encodes a transcription factor required for proliferation and survival of normal myeloid progenitors and leukemic blast cells. Targeting of c-Myb by antisense oligodeoxynucleotides has suggested that myeloid leukemia blasts (including chronic myelogenous leukemia [CML]–blast crisis cells) rely on c-Myb expression more than normal progenitors, but a genetic approach to assess the requirement of c-Myb by p210BCR/ABL-transformed hematopoietic progenitors has not been taken. We show here that loss of a c-Myb allele had modest effects (20%-28% decrease) on colony formation of nontransduced progenitors, while the effect on p210BCR/ABL-expressing Lin− Sca-1+ and Lin− Sca-1+Kit+ cells was more pronounced (50%-80% decrease). Using a model of CML-blast crisis, mice (n = 14) injected with p210BCR/ABL-transduced p53−/−c-Mybw/w marrow cells developed leukemia rapidly and had a median survival of 26 days, while only 67% of mice (n = 12) injected with p210BCR/ABL-transduced p53−/−c-Mybw/d marrow cells died of leukemia with a median survival of 96 days. p210BCR/ABL-transduced c-Mybw/w and c-Mybw/d marrow progenitors expressed similar levels of the c-Myb–regulated genes c-Myc and cyclin B1, while those of Bcl-2 were reduced. However, ectopic Bcl-2 expression did not enhance colony formation of p210BCR/ABL-transduced c-Mybw/d Lin−Sca-1+Kit+ cells. Together, these studies support the requirement of c-Myb for p210BCR/ABL-dependent leukemogenesis.
Designing multiple degenerate primers via consecutive pairwise alignments
Authors: Najafabadi Hamed Shateri , Torabi Noorossadat , Chamankhah Mahmood
Published: January 2008

Background

Different algorithms have been proposed to solve various versions of degenerate primer design problem. For one of the most general cases, multiple degenerate primer design problem, very few algorithms exist, none of them satisfying the criterion of designing low number of primers that cover high number of sequences. Besides, the present algorithms require high computation capacity and running time.

Results

PAMPS, the method presented in this work, usually results in a 30% reduction in the number of degenerate primers required to cover all sequences, compared to the previous algorithms. In addition, PAMPS runs up to 3500 times faster.

Conclusion

Due to small running time, using PAMPS allows designing degenerate primers for huge numbers of sequences. In addition, it results in fewer primers which reduces the synthesis costs and improves the amplification sensitivity.
Signature Evaluation Tool (SET): a Java-based tool to evaluate and visualize the sample discrimination abilities of gene expression signatures
Authors: Jen Chih-Hung , Yang Tsun-Po , Tung Chien-Yi , Su Shu-Han , Lin Chi-Hung , Hsu Ming-Ta , Wang Hsei-Wei
Published: January 2008

Background

The identification of specific gene expression signature for distinguishing sample groups is a dominant field in cancer research. Although a number of tools have been developed to identify optimal gene expression signatures, the number of signature genes obtained is often overly large to be applied clinically. Furthermore, experimental verification is sometimes limited by the availability of wet-lab materials such as antibodies and reagents. A tool to evaluate the discrimination power of candidate genes is therefore in high demand by clinical researchers.

Results

Signature Evaluation Tool (SET) is a Java-based tool adopting the Golub's weighted voting algorithm as well as incorporating the visual presentation of prediction strength for each array sample. SET provides a flexible and easy-to-follow platform to evaluate the discrimination power of a gene signature. Here, we demonstrated the application of SET for several purposes: (1) for signatures consisting of a large number of genes, SET offers the ability to rapidly narrow down the number of genes; (2) for a given signature (from third party analyses or user-defined), SET can re-evaluate and re-adjust its discrimination power by selecting/de-selecting genes repeatedly; (3) for multiple microarray datasets, SET can evaluate the classification capability of a signature among datasets; and (4) by providing a module to visualize the prediction strength for each sample, SET allows users to re-evaluate the discrimination power on mis-grouped or less-certain samples. Information obtained from the above applications could be useful in prognostic analyses or clinical management decisions.

Conclusion

Here we present SET to evaluate and visualize the sample-discrimination ability of a given gene expression signature. This tool provides a filtration function for signature identification and lies between clinical analyses and class prediction (or feature selection) tools. The simplicity, flexibility and brevity of SET could make it an invaluable tool for marker identification in clinical research.
Meta-analysis of breast cancer microarray studies in conjunction with conserved cis-elements suggest patterns for coordinate regulation
Authors: Smith David D , Sætrom Pål , Snøve Ola , Lundberg Cathryn , Rivas Guillermo E , Glackin Carlotta , Larson Garrett P
Published: January 2008

Background

Gene expression measurements from breast cancer (BrCa) tumors are established clinical predictive tools to identify tumor subtypes, identify patients showing poor/good prognosis, and identify patients likely to have disease recurrence. However, diverse breast cancer datasets in conjunction with diagnostic clinical arrays show little overlap in the sets of genes identified. One approach to identify a set of consistently dysregulated candidate genes in these tumors is to employ meta-analysis of multiple independent microarray datasets. This allows one to compare expression data from a diverse collection of breast tumor array datasets generated on either cDNA or oligonucleotide arrays.

Results

We gathered expression data from 9 published microarray studies examining estrogen receptor positive (ER+) and estrogen receptor negative (ER-) BrCa tumor cases from the Oncomine database. We performed a meta-analysis and identified genes that were universally up or down regulated with respect to ER+ versus ER- tumor status. We surveyed both the proximal promoter and 3' untranslated regions (3'UTR) of our top-ranking genes in each expression group to test whether common sequence elements may contribute to the observed expression patterns. Utilizing a combination of known transcription factor binding sites (TFBS), evolutionarily conserved mammalian promoter and 3'UTR motifs, and microRNA (miRNA) seed sequences, we identified numerous motifs that were disproportionately represented between the two gene classes suggesting a common regulatory network for the observed gene expression patterns.

Conclusion

Some of the genes we identified distinguish key transcripts previously seen in array studies, while others are newly defined. Many of the genes identified as overexpressed in ER- tumors were previously identified as expression markers for neoplastic transformation in multiple human cancers. Moreover, our motif analysis identified a collection of specificcis-acting target sites which may collectively play a role in the differential gene expression patterns observed in ER+ versus ER- breast cancer tumors. Importantly, the gene sets and associated DNA motifs provide a starting point with which to explore the mechanistic basis for the observed expression patterns in breast tumors.
E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI)
Authors: Puigbò Pere , Bravo Ignacio G , Garcia-Vallvé Santiago
Published: January 2008

Background

The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values.

Results

The E-CAI server, available at http://genomes.urv.es/CAIcal/E-CAI, is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ) section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue) and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated.

Conclusion

The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences.
Bunched, the Drosophilahomolog of the mammalian tumor suppressor TSC-22, promotes cellular growth
Authors: Gluderer Silvia , Oldham Sean , Rintelen Felix , Sulzer Andrea , Schütt Corina , Wu Xiaodong , Raftery Laurel A , Hafen Ernst , Stocker Hugo
Published: January 2008

Background

Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In Drosophila, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called bunched (bun).

Results

We have identified bun in an unbiased genetic screen for growth regulators in Drosophila. Rather unexpectedly, bun mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA – but not the short isoforms BunB and BunC – is essential and affects growth. Whereas reducing bunA function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes bunA function.

Conclusion

Our findings establish a growth-promoting function of Drosophila BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein.
The cyanobacterial endosymbiont of the unicellular algae Rhopalodia gibba shows reductive genome evolution
Authors: Kneip Christoph , Voβ Christine , Lockhart Peter J , Maier Uwe G
Published: January 2008

Background

Bacteria occur in facultative association and intracellular symbiosis with a diversity of eukaryotic hosts. Recently, we have helped to characterise an intracellular nitrogen fixing bacterium, the so-called spheroid body, located within the diatom Rhopalodia gibba. Spheroid bodies are of cyanobacterial origin and exhibit features that suggest physiological adaptation to their intracellular life style. To investigate the genome modifications that have accompanied the process of endosymbiosis, here we compare gene structure, content and organisation in spheroid body and cyanobacterial genomes.

Results

Comparison of the spheroid body's genome sequence with corresponding regions of near free-living relatives indicates that multiple modifications have occurred in the endosymbiont's genome. These include localised changes that have led to elimination of some genes. This gene loss has been accompanied either by deletion of the respective DNA region or replacement with non-coding DNA that is AT rich in composition. In addition, genome modifications have led to the fusion and truncation of genes. We also report that in the spheroid body's genome there is an accumulation of deleterious mutations in genes for cell wall biosynthesis and processes controlled by transposases. Interestingly, the formation of pseudogenes in the spheroid body has occurred in the presence of intact, and presumably functional, rec A and rec F genes. This is in contrast to the situation in most investigated obligate intracellular bacterium-eukaryote symbioses, where at least either rec A or rec F has been eliminated.

Conclusion

Our analyses suggest highly specific targeting/loss of individual genes during the process of genome reduction and establishment of a cyanobacterial endosymbiont inside a eukaryotic cell. Our findings confirm, at the genome level, earlier speculation on the obligate intracellular status of the spheroid body in Rhopalodia gibba. This association is the first example of an obligate cyanobacterial symbiosis involving nitrogen fixation for which genomic data are available. It represents a new model system to study molecular adaptations of genome evolution that accompany a switch from free-living to intracellular existence.
Microsatellite-based phylogeny of Indian domestic goats
Authors: Rout Pramod K , Joshi Manjunath B , Mandal Ajoy , Laloe D , Singh Lalji , Thangaraj Kumarasamy
Published: January 2008

Background

The domestic goat is one of the important livestock species of India. In the present study we assess genetic diversity of Indian goats using 17 microsatellite markers. Breeds were sampled from their natural habitat, covering different agroclimatic zones.

Results

The mean number of alleles per locus (NA) ranged from 8.1 in Barbari to 9.7 in Jakhrana goats. The mean expected heterozygosity (He) ranged from 0.739 in Barbari to 0.783 in Jakhrana goats. Deviations from Hardy-Weinberg Equilibrium (HWE) were statistically significant (P < 0.05) for 5 loci breed combinations. The DAmeasure of genetic distance between pairs of breeds indicated that the lowest distance was between Marwari and Sirohi (0.135). The highest distance was between Pashmina and Black Bengal. An analysis of molecular variance indicated that 6.59% of variance exists among the Indian goat breeds. Both a phylogenetic tree and Principal Component Analysis showed the distribution of breeds in two major clusters with respect to their geographic distribution.

Conclusion

Our study concludes that Indian goat populations can be classified into distinct genetic groups or breeds based on the microsatellites as well as mtDNA information.
Amplification biases: possible differences among deviating gene expressions
Authors: Degrelle Séverine A , Hennequet-Antier Christelle , Chiapello Hélène , Piot-Kaminski Karine , Piumi Francois , Robin Stéphane , Renard Jean-Paul , Hue Isabelle
Published: January 2008

Background

Gene expression profiling has become a tool of choice to study pathological or developmental questions but in most cases the material is scarce and requires sample amplification. Two main procedures have been used: in vitro transcription (IVT) and polymerase chain reaction (PCR), the former known as linear and the latter as exponential. Previous reports identified enzymatic pitfalls in PCR and IVT protocols; however the possible differences between the sequences affected by these amplification defaults were only rarely explored.

Results

Screening a bovine cDNA array dedicated to embryonic stages with embryonic (n = 3) and somatic tissues (n = 2), we proceeded to moderate amplifications starting from 1 μg of total RNA (global PCR or IVT one round). Whatever the tissue, 16% of the probes were involved in deviating gene expressions due to amplification defaults. These distortions were likely due to the molecular features of the affected sequences (position within a gene, GC content, hairpin number) but also to the relative abundance of these transcripts within the tissues. These deviating genes mainly encoded housekeeping genes from physiological or cellular processes (70%) and constituted 2 subsets which did not overlap (molecular features, signal intensities, gene ID). However, the differential expressions identified between embryonic stages were both reliable (minor intersect with biased expressions) and relevant (biologically validated). In addition, the relative expression levels of those genes were biologically similar between amplified and unamplified samples.

Conclusion

Conversely to the most recent reports which challenged the use of intense amplification procedures on minute amounts of RNA, we chose moderate PCR and IVT amplifications for our gene profiling study. Conclusively, it appeared that systematic biases arose even with moderate amplification procedures, independently of (i) the sample used: brain, ovary or embryos, (ii) the enzymatic properties initially inferred (exponential or linear) and (iii) the preliminary optimization of the protocols. Moreover the use of an in-house developed array, small-sized but well suited to the tissues we worked with, was of real interest for the search of differential expressions.
Relationship between mRNA secondary structure and sequence variability in Chloroplast genes: possible life history implications
Authors: Krishnan Neeraja M , Seligmann Hervé , Rao Basuthkar J
Published: January 2008

Background

Synonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in mitochondrial genes that mutations at third codon position nucleotides in helices are more selected against than those in loops. This motivated us to explore the constraints imposed by mRNA secondary structure on evolutionary variability at all codon positions in general, in chloroplast systems.

Results

We found that the evolutionary variability and intrinsic secondary structure stability of these sequences share an inverse relationship. Simulations of most likely single nucleotide evolution in Psilotum nudum and Nephroselmis olivacea mRNAs, indicate that helix-forming propensities of mutated mRNAs are greater than those of the natural mRNAs for short sequences and vice-versa for long sequences. Moreover, helix-forming propensity estimated by the percentage of total mRNA in helices increases gradually with mRNA length, saturating beyond 1000 nucleotides. Protection levels of functionally important sites vary across plants and proteins: r-strategists minimize mutation costs in large genes; K-strategists do the opposite.

Conclusion

Mrna length presumably predisposes shorter mRNAs to evolve under different constraints than longer mRNAs. The positive correlation between secondary structure protection and functional importance of sites suggests that some sites might be conserved due to packing-protection constraints at the nucleic acid level in addition to protein level constraints. Consequently, nucleic acid secondary structure a priori biases mutations. The converse (exposure of conserved sites) apparently occurs in a smaller number of cases, indicating a different evolutionary adaptive strategy in these plants. The differences between the protection levels of functionally important sites for r- and K- strategists reflect their respective molecular adaptive strategies. These converge with increasing domestication levels of K-strategists, perhaps because domestication increases reproductive output.