bluuebunny/crossref_metadata_2025 huggingface dataset:
The TERI ENVIS Centre: an Indian information centre on renewable energy and the environment
Authors: Bhattacharya P. K. , Ganguly S.
Published: August 2006

Realizing the dearth of environmental information in India, the Ministry of Environment and Forests established an Environmental Information System (ENVIS) as a plan programme in December 1982. The focus of ENVIS since its inception has been on providing environmental information to decision makers, policy planners, scientists and engineers, research workers, etc., all over India. Under this programme a few organizations were identified as centres of excellence and requested to host ENVIS Centres on various environmental areas. The Energy and Resources Institute (TERI) in New Delhi was identified as the ENVIS Centre on Renewable Energy and Environment. This paper highlights the activities performed at the TERI ENVIS Centre and the various tools used, such as web sites, publications, etc., to disseminate information among researchers, consultants and policy makers. It also outlines future courses of action for the Centre.
Integrating ICTs into the Globalization of the Poor Developing Countries
Authors: Nwagwu Williams Ezinwa
Published: August 2006

The impact of ICTs in developing countries generally can be considered inegalitarian because their benefits accrue more to the rich than the poor developing countries, thus defining a new form of digital divide. Certain ICT-induced developments such as globalization tend to leave the poor developing countries behind the global development agenda. In this article, we recognize the need for global-scale countervailing policies to establish the true pattern and structure of poverty and ICTs consumption and utilization in the developing countries in order to determine how the ICTs-heavy activities of the rich developing countries can be aligned with the ICTs needs of the poor developing countries. This will help ensure that ICTs are contributing in the development and globalization of the poor countries. The article recommends strategies that can be adopted to boost the participation of poor developing countries in the globalization process.
Using the Online Public Access Catalogue at the University of Botswana
Authors: Morupisi L. , Mooko N. P.
Published: August 2006

Reports on a study aimed at assessing the use of the online public access catalogue (OPAC) by students doing sociology courses at the University of Botswana. The objectives of the study were to establish: the types of search strategies used by students when searching OPAC; the problems encountered during searches; whether students were able to retrieve records related to their topics of research; if students were satisfied with the outcome of the searches. A questionnaire and observation were used to collect data. The findings indicated that respondents searched mostly by title, author, keyword and subject. They had difficulties with subject search, use of advanced searching options, downloading and printing search results, accessing full-text journal articles through OPAC, lack of Internet access on campus, lack of access to computers because they are always occupied by other students, and the OPAC often being down.
To the Moon, Mars, and Beyond: Culture, Law, and Ethics in Space-Faring Societies
Authors: Billings Linda
Published: August 2006

The U.S. civilian space program is focused on planning for a new round of human missions to the Moon and, later, perhaps, to Mars. These plans are intended to realize a “vision” for exploration articulated by President George W. Bush. It is important to examine this “vision” in the broader context of 21st-century space exploration, which is a truly global enterprise. Questions to be addressed include the following: How will extending human presence into the solar system affect society and culture on Earth? What legal, ethical, and other value systems should govern human settlements and other activities in space? Do humans have rights to exploit extraterrestrial resources and alter extraterrestrial environments? Does space exploration need reinvention to meet social needs? This article describes the current environment for space policy making and a framework of space law, ethics, and culture within which these questions can be considered.
Community Networks and Public Participation: A Forum for Civic Engagement or a Platform for Ranting Irate Malcontents?
Authors: Ferber Paul , Foltz Franz , Pugliese Rudy
Published: August 2006

Forums of public discussion on Internet Web sites have been promoted by some as having the potential to improve democracy through large increases in civic engagement. Such claims are scoffed at by others. To date, such forums tend to be found more on community networks and commercial Web sites than on sites owned by governments. We thus turn to an examination of forums hosted by a private New Jersey organization, to seek to understand the types and character of discussion taking place. Discussion of politics and government, especially at the local level, represented slightly more than one half of the postings. Participation in the forums, however, appeared limited to a small number of people.
Governance Challenges of Technological Systems Convergence
Authors: Whitman Jim
Published: August 2006

The convergence of several technological systems (especially nanotechnology, biotechnology, information technology, and robotics) has now been adopted as a strategic goal by several countries, most notably the United States and those of the European Union. The anticipated benefits and related fears of competitive disadvantage have brought together a wide range of interested parties, governmental and nongovernmental. In the rush to enter and/or dominate this arena, the benign promise of converging technologies (CT) are highlighted, although a range of risks and less welcome (if difficult to quantify) implications are at best understated. What, then, are the prospects for exercising governance over the technological systems we are busy creating—and the uses to which they might be put? What will it mean to speak of “global governance” in a world in which the technological promise of CT has been fulfilled?
Confronting the Spirit of Our Age as a Creator of Chaos
Authors: Vanderburg Willem H.
Published: August 2006

Contemporary civilization has created a fundamental contradiction between the intellectual approach to knowing and the technical approach to doing on the one hand, and the results of their application on the other. These approaches to knowing and doing begin with a process of abstraction that trades breadth for depth, while their application reveals a multitude of problems associated with ignoring the fact that everything is related to everything else in our world. Scientific disciplines and technical specialties create “pure” domains of investigation “uncontaminated” by interactions with all other domains, thereby distorting the internal fabric of relations and its connections with everything else. Hence, the most powerful means humanity has ever created are indissociably linked with the production of chaos in human life, society, and the biosphere. A new domain of study is needed to the interactions between society, technology, science, and the biosphere (STSB). The scope, direction, and methodological challenges are briefly examined, and the possible mission of STSB within the contemporary university.
Evolution and Online Instruction: Using a Grounded Metaphor to Explore the Advantageous and Less Advantageous Characteristics of Online Instruction
Authors: Campbell Todd
Published: August 2006

This research presents a case study of the first-time experience of the instructor-researcher in teaching an online class. Through thematic analysis and grounded metaphor, evolution was identified as the metaphor used to illuminate the emerging themes in creating a narrative. Advantageous and less-than-advantageous characteristics of online instruction were identified. The advantageous characteristics identified were (a) students actively involved in their own education, assessing their own learning and seeking additional information; (b) students constructing knowledge; (c) measured responses by students; (d) an increase in the quality of students work because of open access to peers' work; and (e) students' increases in technological confidence. The less-than-advantageous characteristics found were (a) concerns for clarity, (b) concerns for loss of personal or intimate interactions, and (c) misinterpretations resulting from communicating online. It is hoped that this work will assist the in understanding and the continued investigation of online instruction.
Confessions of a Shoveler: STS Subcultures and Engineering Ethics
Authors: Herkert Joseph R.
Published: August 2006

Mainstream science, technology, and society scholars have shown little interest in engineering ethics, one going so far as to label engineering ethics activists as “shit shovelers.” Detachment from engineering ethics on the part of most STS scholars is related to a broader and long-standing split between the scholar-oriented and activist-oriented wings of STS. This article discusses the various STS “subcultures” and argues that the much-maligned activist STS subculture is far more likely than the mainstream scholar subculture to have a significant impact on engineering ethics education and practice.
Crime, Prostitution, Drugs, and Malingered Insanity
Authors: Geiger Brenda
Published: August 2006

Mizrahi female offenders have been described as passive victims propelled into crime, prostitution, and drug abuse as a result of traumatic childhood and life course experiences. This qualitative study adopts a postmodern critical orientation and Foucault's bottom-up microsocial analysis of power to examine the trajectories of resistance of 8 female offenders who break the silence to tell their life story. Analysis of narratives, informal conversations, and more focused, in-depth interviews with these women allow the deconstruction of the stereotype of the passive and helpless female offender. Using the sensitizing concepts of control, agency, and resistant efforts and letting the data speak, this research reconstructs female offending as a hidden script of resistance against intolerable socioeconomic deprivation and extreme forms of abuse.
Work and Slave Family Life in Antebellum Northern Virginia
Authors: Pargas Damian Alan
Published: August 2006

Work patterns and the nature of regional agriculture defined the world of antebellum slave families in the American South. This article examines the effects that work had on the collective experiences of slave families living in Fairfax County in northern Virginia. Specifically, this study explores the consequences of work for child rearing, family time, and the development of internal family economies among slave families. A region often overlooked by historians of the antebellum South, northern Virginia was a difficult place for slave families by any standard. As this study will show, a weak agricultural sector and small slaveholdings, combined with long workdays, forced slaves to resort to shared child rearing and offered families few opportunities to be together or to develop extensive family economies.
Work-related travel, gender and family obligations
Authors: Gustafson Per
Published: August 2006

This article uses national travel surveys from Sweden to examine the relationship between family situation, sex and work-related overnight travel. The results indicate that family obligations have an impact on travel activity, but that women and men differ in this respect. Cohabiting men travel more than men living alone, whereas there is no such effect among women. Having young children reduces the travel activity of women, whereas there is no consistent such effect among men. However, regardless of family situation, men travel considerably more than women and this largely reflects women’s and men’s different positions in working life. It is therefore argued that the relationship between work-related travel and family obligations involves both individual adaptation and structural factors, such as a gender-segregated labour market and ‘gender-typing’ of travel as a predominantly male activity, all of which reflect traditional gender and family role expectations.
The Personality of Followers and its Effect on the Perception of Leadership
Authors: Schyns Birgit , Felfe Jörg
Published: August 2006

This article focuses on the way in which followers' personality characteristics shape their perception of transformational leaders. After a review of prior research, a study using a U.S. employee sample is presented in which follower extraversion and agreeableness are found to be related to the perception of transformational leadership. On the basis of this research, the authors formulate questions concerning the relationship between followers' personality and the perception of transformational leadership. With reference to these questions, the authors outline an agenda for future research.
360-Degree Feedback to Leaders
Authors: Atwater Leanne E. , Brett Joan F.
Published: August 2006

This study examined the extent to which changes in leader behavior 1 year after a 360-degree feedback intervention related to changes in employee attitudes. Participants were 145 leaders and their subordinates, peers, and manager. The results indicated that improved subordinate ratings of the leader on consideration, performance orientation, and employee development related to increased subordinate engagement and satisfaction as well as reduced intentions to leave following 360-degree feedback to leaders. This study demonstrates that improved leader behavior following 360-degree feedback is related to improved employee attitudes.
Ambiguous Loss and the Family Grieving Process
Authors: Betz Gabrielle , Thorngren Jill M.
Published: August 2006

Ambiguous losses are physical or psychological experiences of families that are not as concrete or identifiable as traditional losses such as death. Ambiguous loss could include anything from miscarriage to losing one's spouse to Alzheimer's disease while he or she is still living. Ambiguous loss may include not knowing whether or not a loved one is living or dead, such as cases of child abduction or military personnel who are missing in action. Ambiguous loss is inherently characterized by lack of closure or clear understanding. This article defines types of ambiguous losses and details some of their characteristics. A model for counseling families who are experiencing ambiguous loss is described. Specifically, the model combines family stress theory with narrative therapy techniques to help families define their losses, assess their resources, and develop meaningful narratives about the loss.
New Mothers and Sexual Intimacy: An Existential Framework for Counseling
Authors: Adams Lisa G. , Harper Amney J. , Johnson Elise P. , Cobia Debra C.
Published: August 2006

A review of the existing literature reveals limited understanding of and guidance for the treatment of decreased sexual intimacy among new mothers. The authors apply key concepts from existentialism as a theoretical framework to address these limitations. From this perspective, variables affecting sexual intimacy among new mothers are identified and discussed in the context of the natural, personal, social, and spiritual dimensions of being. Corresponding suggestions for treatment are provided.
Research on Divorce Among Postsecondary Students: Surprisingly Missing
Authors: Galvin Christina Rosen
Published: August 2006

The rigors of university life can be demanding, especially with non-traditional students juggling multiple responsibilities such as being a student, parent, and/or spouse, and working full-time. Such responsibilities can affect couple relationships and marriages. This article reviews the research literature on divorce among postsecondary students. Implications for practitioners and future research are also presented.
Self-Injury and Postvention: Responding to the Family in Crisis
Authors: Trepal Heather C. , Wester Kelly L. , MacDonald Colleen A.
Published: August 2006

Postvention actions are commonly employed after completed suicides and suicide attempts but can be adapted to assist affected family members in dealing with other types of crisis. The authors adapt a postvention model to be applied to systemically working with families who have a member engaging in self-injurious behavior. Recommendations for counselors who work with youth who self-injure and their families are provided.
Inside Memory
Authors: Berikoff Ahna
Published: August 2006

The following is a story of the author and her mother. This story takes place within a small social and cultural movement of the Sons of Freedom Doukhobors. Through a coconstructed narrative, the author captures personal discourses, thoughts, and memories extending throughout 30 years. Their experiences and distinct cultural locations reflect a tenacity to preserve cultural identity while struggling to maintain their relationship. Throughout the story are glimpses of history, which is woven into their lives. The author demonstrates how culture, tradition, and motivation transmit the spirit of their ancestors into the present. The author looks at how present and past share time and space, in spirit and in action.
Not Quite Acceptable
Authors: Brogden Lace Marie
Published: August 2006

Re:membering can be used as a research tool for messing with notions of “self.” As a tool of autobiographical narrative, textual fragments may be useful in peacing/piecing together some ways in which memories efface and, alternatively, reinscribe themselves on postcetera (including, but not limited to, postmodern, poststructural, and postcolonial) identities. This article is inspired by two previous works by James Haywood Rolling, Jr., published in Qualitative Inquiry: “Messing Around With Identity Constructs: Pursuing a Poststructuralist and Poetic Aesthetic” and “Searching Self-Image: Identities to Be Self-Evident.” Through the use of bricolage as method, it is written as a response to “death” and as a re:generation of possibilities for disrupting identity constructs with/in autobiographical research writing.
Representin(g)
Authors: Hill Marc Lamont
Published: August 2006

In this article, the author examines the dilemmas that emerged in his role as teacher-researcher in Hip-Hop Lit, a hip-hop-centered literature class within an evening education program. Specifically, the author examines the complex and often competing roles and identities that he performed within the research context, as well as during the process of ethnographic writing. The author details how these roles and identities were mediated by the various allegiances, commitments, and beliefs that prompted the study, as well as those that developed in response to the relationships that were forged with research participants. The article argues for a constant reflection on and response to issues of identity, authority, and power while in the field and “behind the desk.”
Dilemmas, Maintaining “Face,” and Paranoia
Authors: Jones Robyn
Published: August 2006

The purpose of this article is to tell a different, perhaps a “truer,” story about coaches and coaching through presenting an autoethnography of the author as a dysfluent coach. The author’s tale, which depicts a typical pregame scenario, explores issues associated with maintaining “face” and others’ respect in a context characterized by uncertainty, ambiguity, and power. In addition, within the endnotes, the applicability of the storied genre to coaching research is discussed, with Goffman’s works on stigma, interaction, and impression management offered as theoretical signposts to help readers better interpret the author’s account.
Stories I Live By
Authors: Lewis P. J.
Published: August 2006

In this work, narrative provides the framework and storytelling, the act. Storytelling is woven through the narrative presentation of story making as meaning making. It is an attempt to show rather than to tell what stories do. It entwines the ontological and epistemological position of narrative with the demonstrative use of storytelling to exemplify the primacy of narrative in meaning making. Narrative and storytelling work together to create meaning and metameaning through story and projection. Come, listen to some stories.
Encounters and Directions in Research
Authors: Watson Cate
Published: August 2006

This article is a companion piece to a presentation given at the 19th Annual Conference on Interdisciplinary Studies 2006 (University of Georgia), at which I read extracts from my simulacrum reflective journal—performing a narrative about narrative research. Narratives of research, like all narratives, are a means by which we impose order on a chaotic world. But narratives also function to subvert that order, to undermine the commonplace and the canonical. It is the appearance of the unexpected from which the narrative emerges. The journal facilitates this process of narrative construction, enabling a creative exploration of concepts and ideas, functioning at both a content level and supporting “writing as a method of inquiry.” The article illustrates this, its purpose to subvert, but extend, understandings about the processes involved in doing “being a researcher.”
Toward an Inquiry of Discomfort
Authors: Wolgemuth Jennifer R. , Donohue Richard
Published: August 2006

This article argues for conducting emancipatory narrative research with the explicit intent of transforming participants’ lives by opening up new subjective possibilities. Drawing from Megan Boler’s pedagogy of discomfort and Gubrium and Holstein’s active interviewing, a narrative research method called an inquiry of discomfort is proposed. An inquiry of discomfort emphasizes the proactive and transformative potential of research projects for both researcher and participant. The aim of an inquiry of discomfort is to identify and promote a beneficial shift from dualistic, categorical, and entrenched subjective positionality to a more ambiguous engagement with social reality. The argument is considered in light of preliminary empirical findings from a narrative pilot study of masculine heterosexual subjectivity in graduate education, conducted in the fall of 2003. Based on theoretical and empirical evidence, the general features of an inquiry of discomfort within an emancipatory narrative study are presented.
Making Beautiful
Authors: Ahmed S. M. Faizan
Published: August 2006

Many competing sociological debates intersect in the world of beauty parlors. There is an increasing proliferation of male or “gents” parlors—a space where a new formation of the male self is being produced and established through new cultures of care and work. Because “work” has always been understood as central to the lives of men, a major basis of their identity, it is often seen as being identified with masculinity. “Beauty” and “caring,” on the other hand, are often viewed as something intrinsically feminine. This article weeds out such notions by presenting life histories of men in “beauty work” and argues that just as different work situations produce different models of masculinities, the same work situation also may prove an arena of a variety of masculinities. The article also explores the possibilities and potentials of understanding gender relations in South Asia that will prove helpful in making comparisons with other masculinity studies.
Invisible Men
Authors: Chopra Radhika
Published: August 2006

This article addresses the issue of gendering the veil and argues that veiling must expand beyond the primary focus on clothing and must be viewed as a system that frames bodily styles, speech forms, and the language of gestures. Veiling has feminine and masculine forms but evokes different things for men and women and is experienced in dualgendered ways. The ethnography focuses on the lives of male domestic workers who are liminal and incomplete members of contemporary urban households to address the issue of the performance of maleness and male veiling practices by the partial members of social units such as households to argue that we must understand veiling as a way of undoing gender. The intersections of class, sexuality, and gender within interior spaces of domesticity reconfigure relations of gender. Work as a site within which masculinity, identity, and power are constituted enables us to view male veiling beyond the shame and honor discourse to address the bodies and dispositions of men who labor.
Best practice in smoking cessation services for pregnant women: results of a survey of three services reporting the highest national returns, and three beacon services
Authors: Lee Michelle , Hajek Peter , McRobbie Hayden , Owen Lesley
Published: August 2006

Aims: The NHS allocated dedicated funds to establish specialist smoking cessation services for pregnant smokers in England in 2000. An early survey revealed some uncertainty as to how the new services should work and monitor their outcome. The current survey focused on identifying examples of good practice in this difficult new field.

Method: Three services with the highest number of successful four-week quitters reported for the 2003/4 monitoring year were identified from Department of Health (DH) monitoring records, and three services were nominated from those known in the field as examples of best practice. There was no overlap between the two groups. All six services provided in-depth interviews.

Results: All three highest ranking services that reported close to 100 per cent success rates included unaided quitters identified from hospital wards, rather then smokers actually treated. They had only minimal or average genuine treatment provision for pregnant smokers in place. The three beacon services far exceeded the national throughput and outcome average identified in the previous survey, and provided a wealth of useful information. Although they differed in staffing levels and other aspects of their activities, they all shared several key elements, including a systematic training of midwives in how to refer pregnant smokers, offering nicotine replacement treatment to almost all clients and having an efficient system of providing the prescriptions, offering flexible home visits, and providing intensive multi-session treatment delivered by a small number of dedicated staff.

Conclusion: Smoking cessation services for pregnant women may need clearer guidance on what they are expected to provide, and how they should monitor their outcome. The key features of the beacon services can serve as a practical model of current best practice applicable across most PCTs.
The Future of Evidence in Evidence-based Practice
Authors: Magill Molly
Published: August 2006

Summary: This article considers factors important to the broad-scale adoption of an evidence-based approach to social work practice (EBP). Elements of the EBP framework, and particularly directions for future research, are examined in terms of a number of criticisms voiced in the literature.

Findings: Scholars in social work and allied disciplines have emphasized the implications of evidential hierarchies, and particularly the questionable clinical relevance of randomized controlled trials. While offering important considerations, arguments in opposition of EBP can be misconceived. Evidence-based practice is not merely a ‘best practice’ orientation, but a heuristic framework intended to foster explicit and accountable decisional capacities. Where EBP is limited highlights empirical questions that remain unanswered. Future directions for the approach will require the participation of both practitioners and researchers.

Applications: The article delineates the role of operationalized clinical decision-making, local clinical research, and the unique utilities of evaluation methodologies in building knowledge for a more clinically relevant evidence-base for social work practice.
Parents, Professionals, and Paranoia
Authors: Piper Heather , Powell John , Smith Hannah
Published: August 2006

Summary: In this paper, we appeal to professionals and others to take a more considered approach to the increasing panic relating to the touching of children of all ages. We attempt to disrupt the current trend by drawing attention to that which is currently being deferred in professional practice, yet which is evident in many formal and informal guidelines. We suggest that the contradictions we identify throughout the paper result more from a culture of fear than one of caring. We draw on our own small-scale earlier research experiences, and relevant and related literature in the area, but also note a scarcity of both in the UK context. We conclude that touching, at least in anglicized societies, has become an area that now requires fine judgements dependent on the interactive processes between all parties and that a broad-based analysis is clearly required. But we consider hesitation and ambiguity to be unavoidable in ethical decision making, something to be encouraged and not avoided by the search for blueprints, in our attempts to manage the perceived ‘risks’.

Findings: Current practice is more dependent on fears of accusation and litigation than any concern for a child. Most child care workers ‘know’ this on the one hand, but nevertheless still attempt to justify their actions as sensible decision making. For example, a play group leader will claim he or she can’t put a plaster on a child because of a potential allergy: this is in spite of completed forms requesting information relating to allergies for each child, and allergies cease to be an issue anyway when a child is taken to the medical box and instructed from a distance on how to apply a plaster themselves. Contradictory accounts such as this are abundant in this area, and we suggest that many workers are behaving more like ‘victims’ than professionals.

Applications: This paper is concerned with drawing attention to the need for all professionals working with children and young people of all ages to question their current and future decision making in relation to the wide range of touching practices that occur on a daily basis. Professionals should make their own mind up in relation to ethical matters, remembering that the ‘radicals’ of today become the ‘liberals’ of tomorrow.
The Influence of Grades on Teaching Effectiveness Ratings at a Hispanic-Serving Institution
Authors: Guinn Bobby , Vincent Vern
Published: August 2006

The study's purpose was to extend the research dealing with the influence of grades on student evaluation of teaching (SET). Fifty-four college faculty served as study participants. Discriminate analysis indicated that a student with a higher expected course grade would give a higher SET rating of teaching effectiveness. This finding is consistent with that reported at institutions with predominantly White, non-Hispanic enrollments.
Substantive Members Should Receive Financial Aid
Authors: Perry Andre M.
Published: August 2006

Policy makers have not reached a reasonable consensus on whether undocumented immigrants should receive financial aid nor developed a consistent set of conditions for eligibility. This article builds on an earlier case study and explores some of the critical issues that prevent actors from creating policy that reflects our underlying attitudes of membership. It addresses critical points of tension so that readers and policy makers can possibly reconcile intuitions and actions.
T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFβ dosage.
Authors: Talebian Laleh , Li Zhe , Guo Yalin , Gaudet Justin , Speck Maren E. , Sugiyama Daisuke , Kaur Prabhjot , Pear Warren S. , Maillard Ivan , Speck Nancy A.
Published: August 2006

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4−CD8− double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.
Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors
Authors: Navas Tony A. , Mohindru Mani , Estes Myka , Ma Jing Ying , Sokol Lubomir , Pahanish Perry , Parmar Simrit , Haghnazari Edwin , Zhou Li , Collins Robert , Kerr Irene , Nguyen Aaron N. , Xu Yin , Platanias Leonidas C. , List Alan A. , Higgins Linda S. , Verma Amit
Published: August 2006

The myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38α by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38α isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS.
PKCδ regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation
Authors: Pula Giordano , Schuh Kai , Nakayama Keiko , Nakayama Keiichi I. , Walter Ulrich , Poole Alastair W.
Published: August 2006

Protein kinase Cδ (PKCδ) has been shown by pharmacologic approaches to negatively regulate collagen-induced platelet aggregation. Here we addressed the molecular and cellular mechanisms underlying this negative regulation. Using PKCδ–/– platelets, we show that the mechanism did not involve altered inside-out signaling to integrin αIIbβ3 and did not affect early signaling events downstream of GPVI, because there was no difference in tyrosine phosphorylation of PLCγ2 between wild-type and PKCδ–/– platelets. There was also no increase in secretion of dense granule content, in contrast to studies using rottlerin where secretion was enhanced. Importantly, however, there was marked enhancement of filopodia generation in PKCδ–/– platelets upon adhesion to collagen compared with wild-type platelets. Filopodia play an essential role regulating adhesive events leading to platelet aggregation by increasing platelet-platelet contact. We show that the critical effector for PKCδ is vasodilator-stimulated phosphoprotein (VASP), a major regulator of actin cytoskeleton dynamics. PKCδ physically interacts with VASP constitutively and regulates its phosphorylation on Ser157. In VASP–/– platelets, the enhancement of filopodia generation, actin polymerization, and platelet aggregation by rottlerin is ablated. PKCδ is therefore a critical negative regulator of filopodia, and hence platelet aggregation, through a functional interaction with the actin organizer VASP.
Recording long-term potentiation of synaptic transmission by three-dimensional multi-electrode arrays
Authors: Kopanitsa Maksym V , Afinowi Nurudeen O , Grant Seth GN
Published: August 2006

Background

Multi-electrode arrays (MEAs) have become popular tools for recording spontaneous and evoked electrical activity of excitable tissues. The majority of previous studies of synaptic transmission in brain slices employed MEAs with planar electrodes that had limited ability to detect signals coming from deeper, healthier layers of the slice. To overcome this limitation, we used three-dimensional (3D) MEAs with tip-shaped electrodes to probe plasticity of field excitatory synaptic potentials (fEPSPs) in the CA1 area of hippocampal slices of 129S5/SvEvBrd and C57BL/6J-TyrC-Brdmice.

Results

Using 3D MEAs, we were able to record larger fEPSPs compared to signals measured by planar MEAs. Several stimulation protocols were used to induce long-term potentiation (LTP) of synaptic responses in the CA1 area recorded following excitation of Schäffer collateral/commissural fibres. Either two trains of high frequency tetanic stimulation or three trains of theta-burst stimulation caused a persistent, pathway specific enhancement of fEPSPs that remained significantly elevated for at least 60 min. A third LTP induction protocol that comprised 150 pulses delivered at 5 Hz, evoked moderate LTP if excitation strength was increased to 1.5× of the baseline stimulus. In all cases, we observed a clear spatial plasticity gradient with maximum LTP levels detected in proximal apical dendrites of pyramidal neurones. No significant differences in the manifestation of LTP were observed between 129S5/SvEvBrd and C57BL/6J-TyrC-Brdmice with the three protocols used. All forms of plasticity were sensitive to inhibition ofN-methyl-D-aspartate (NMDA) receptors.

Conclusion

Principal features of LTP (magnitude, pathway specificity, NMDA receptor dependence) recorded in the hippocampal slices using MEAs were very similar to those seen in conventional glass electrode experiments. Advantages of using MEAs are the ability to record from different regions of the slice and the ease of conducting several experiments on a multiplexed platform which could be useful for efficient screening of novel transgenic mice.
Adiponectin-induced secretion of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) is impaired in monocytes from patients with type I diabetes
Authors: Abke Sabine , Neumeier Markus , Weigert Johanna , Wehrwein Gabriele , Eggenhofer Elke , Schäffler Andreas , Maier Kevin , Aslanidis Charalampos , Schölmerich Jürgen , Buechler Christa
Published: August 2006

Background

Systemic adiponectin is reduced in patients with cardiovascular disease (CVD) and low adiponectin may contribute to the pathogenesis of atherosclerosis. However, circulating adiponectin is elevated in type 1 diabetes (T1D) patients, who have also a higher incidence to develop CVD. Because monocytes play an important role in atherosclerosis, we analysed the influence of adiponectin on cytokine and chemokine release in monocytes from T1D patients and controls.

Methods

Systemic adiponectin was determined in the plasma and the high-molecular weight (HMW) form of adiponectin was analysed by immunoblot. Monocytes were isolated from T1D patients and controls and the adiponectin-stimulated release of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) was analysed.

Results

Systemic adiponectin was higher in T1D patients. Immunoblot analysis of the plasma indicate abundance of HMW adiponectin in T1D patients and controls. IL-6, CCL2 and CXCL8 secretion in response to adiponectin were found induced in monocytes from controls whereas only IL-6 was upregulated in T1D cells. The induction of IL-6 by adiponectin was abrogated by an inhibitor of the NFκB pathway.

Conclusion

These data indicate that adiponectin-mediated induction of IL-6, CCL2 and CXCL8 is disturbed in monocytes from T1D patients and therefore elevated systemic adiponectin in T1D patients may be less protective when compared to controls.
Endotoxin-induced myocardial dysfunction in senescent rats
Authors: Rozenberg Sandrine , Besse Sophie , Brisson Hélène , Jozefowicz Elsa , Kandoussi Abdelmejid , Mebazaa Alexandre , Riou Bruno , Vallet Benoît , Tavernier Benoît
Published: August 2006

Introduction

Aging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction.

Methods

Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca2+ sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO2) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated.

Results

LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 ± 4 vs 53 ± 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 ± 7 vs 100 ± 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca2+ sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO2 were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals.

Conclusion

Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca2+-sensitizing agents may not be as effective in aged subjects as in younger subjects.
Regulation of Akt/PKB by phosphatidylinositol 3-kinase-dependent and -independent pathways in B-cell chronic lymphocytic leukemia cells: role of protein kinase Cβ
Authors: Barragán Montserrat , de Frias Mercè , Iglesias-Serret Daniel , Campàs Clara , Castaño Esther , Santidrián Antonio F , Coll-Mulet Llorenç , Cosialls Ana M , Domingo Alicia , Pons Gabriel , Gil Joan
Published: August 2006

Apoptosis of B cell chronic lymphocytic leukemia (B-CLL) cells is regulated by the PI-3K-Akt pathway. In the present work, we have analyzed the mechanisms of Akt phosphorylation in B-CLL cells. Freshly isolated cells present basal Akt phosphorylation, which is PI-3K-dependent, as incubation with the PI-3K inhibitor LY294002 decreased Ser-473 and Thr-308 phosphorylation in most samples analyzed (seven out of 10). In three out of 10 cases, inhibition of protein kinase C (PKC) inhibited basal Akt phosphorylation. Stromal cell-derived factor-1α, IL-4, and B cell receptor activation induced PI-3K-dependent Akt phosphorylation. PMA induced the phosphorylation of Akt at Ser-473 and Thr-308 and the phosphorylation of Akt substrates, independently of PI-3K in B-CLL cells. In contrast, PKC-mediated phosphorylation of Akt was PI-3K-dependent in normal B cells. Finally, a specific inhibitor of PKCβ blocked the phosphorylation and activation of Akt by PMA in B-CLL cells. Taken together, these results suggest a model in which Akt could be activated by two different pathways (PI-3K and PKCβ) in B-CLL cells.
Pivotal Advances: High-mobility group box 1 protein—a cytokine with a role in cardiac repair
Authors: Germani Antonia , Limana Federica , Capogrossi Maurizio C
Published: August 2006

The nuclear protein high-mobility group box 1 (HMGB1) has been largely characterized for its role in inflammation. However, HMGB1 released by inflammatory cells, as well as by necrotic cells, may also act as a signal of tissue damage and participate in tissue repair by recruiting stem cells to the injury site. The emergence of this function has focused the interest on HMGB1 as a molecule with an active role in tissue regeneration. We recently demonstrated that HMGB1 administration in a mouse model of myocardial infarction activates cardiac stem cells and promotes their differentiation into cardiomyocytes. The regenerative effect results in the improvemet of cardiac function. In this review, we highlight the beneficial role of HMGB1 and discuss growth factor-based therapeutic approaches for the treatment of myocardial infarction.
Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis
Authors: Lorenowicz Magdalena J , van Gils Janine , de Boer Martin , Hordijk Peter L , Fernandez-Borja Mar
Published: August 2006

Extravasation of leukocytes is a crucial process in the immunological defense. In response to a local concentration of chemokines, circulating leukocytes adhere to and migrate across the vascular endothelium toward the inflamed tissue. The small guanosinetriphosphatase Rap1 plays an important role in the regulation of leukocyte adhesion, polarization, and chemotaxis. We investigated the role of a guanine nucleotide exchange protein for Rap1 directly activated by cAMP (Epac1) in adhesion and chemotaxis in a promonocytic cell line and in primary monocytes. We found that Epac1 is expressed in primary leukocytes, platelets, CD34-positive hematopoietic cells, and the leukemic cell lines U937 and HL60. Epac activation with an Epac-specific cAMP analog induced Rap1 activation, β1-integrin-dependent cell adhesion, and cell polarization. In addition, activated Epac1 enhanced chemotaxis of U937 cells and primary monocytes. Similar to activation of Epac1, stimulation of cells with serotonin to induce cAMP production resulted in Rap1 activation, increased cell adhesion and polarization, and enhanced chemotaxis. The effects of serotonin on U937 cell adhesion were dependent on cAMP production but could not be blocked by a protein kinase A inhibitor, implicating Epac in the regulation of serotonin-induced adhesion. In summary, our work reveals the existence of previously unrecognized cAMP-dependent signaling in leukocytes regulating cell adhesion and chemotaxis through the activation of Epac1.
Roles of leukocytosis and cysteinyl leukotriene in polymorphonuclear leukocyte-dependent plasma extravasation
Authors: Tokita Kazutaka , Uchida Yasuhiro , Yamamoto Tetsuro
Published: August 2006

The PMN-dependent plasma extravasation is a major mechanism of permeability enhancement in acute inflammation. To reveal the pathophysiological significance of the PMN-dependent plasma extravasation, we prepared a systemic leukocytotic guinea pig model by a daily injection of recombinant human (rh)G-CSF. The extent of the PMN-dependent plasma extravasation, regarded as the late-phase permeability induced by an intradermal injection of zymosan-activated guinea pig plasma (ZAP) or of rhC5a, clearly correlated to the circulating PMN number. The augmentation of local response following the systemic response seemed to be the characteristic feature of the PMN-dependent plasma extravasation. We then revealed the molecular mechanism of the PMN-dependent plasma extravasation. Neither the antihistaminic agent diphenhydramine, nor the bradykinin B2 receptor antagonist, HOE140, affected the ZAP-induced, late-phase extravasation. In contrast to this, pretreatment with an antagonist of cysteinyl leukotriene (cys-LT) 1 receptor, pranlukast, significantly reduced the late-phase extravasation. Similarly, it was reduced by pretreatment with a 5-lipoxygenase inhibitor, MK-886, indicating the participation of cys-LTs in the PMN-dependent plasma extravasation. Histologically, pretreatment with pranlukast or MK-886 did not affect the ZAP-induced PMN infiltration. Consistently, a combined treatment with pranlukast and diphenhydramine completely suppressed the early-phase extravasation. As pranlukast pretreatment did not affect plasma extravasation induced by mast cell degranulation, and depletion of platelets did not influence the pranlukast-inhibitable plasma extravasation induced by rhC5a injection, cys-LTs are most likely produced by transcellular biosynthesis involving PMNs and vascular wall cells.