bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the Work—Class Nexus: Theoretical Foundations for Recent Trends
Authors: Atkinson Will
Published: October 2009

The sociology of class and the sociology of work have, historically, occupied two sides of the same coin, sharing foundational studies such as the Affluent Worker series and Braverman’s vivisection of the labour process. Recently, however, the par tnership has been questioned. Though the seeds of the split were sown by Erik Wright and John Goldthorpe, the overdue de-hegemonizing of Marx and Weber in research on class with the growing influence of Pierre Bourdieu and the broader ‘cultural turn’ in sociology has weakened the bond and forged a new alliance between class and the sociology of culture. This is, by all means, a positive development, but the connection between processes in the sphere of work and class has become less clear. This ar ticle therefore seeks to explore the new theoretical nexus between class and work, demonstrating that a Bourdieusian approach fruitfully reverses the connection put in place by Goldthorpe and Wright.
Work and the Moving Image: Past, Present and Future
Authors: Hindmarsh Jon
Published: October 2009

This article explores some of the similarities and differences between two approaches to the study of work that use moving images. The first approach, most notably practised by Frank and Lillian Gilbreth, ‘dissected’ the movement of workers’ bodies in the pursuit of efficiency. The second approach has emerged in the last few decades from ethnomethodology and conversation analysis. The ar ticle notes how shared technologies for data collection and shared interests in work practice belie more fundamental differences in analytic orientation. The article uses this comparison to highlight the potential contributions that the more recent corpus of studies can make to our understanding of work; an understanding that prioritizes the methodic practices in and through which members of society accomplish, experience and constitute work and organization.
Molds, mycotoxins, and sick building syndrome
Authors: Straus David C
Published: October 2009

The following is a review of some of the work we have done since 2004 regarding the importance of molds and their mycotoxins in the phenomenon of sick building syndrome (SBS). In these studies we showed that the macrocyclic trichothecene mycotoxins (MTM) of Stachybotrys chartarum (SC) are easily dissociated from the surface of the organism as it grows and could therefore be consequently spread in buildings as the fungus experiences additional water events. We then showed that SC and Penicillium chrysogenum (PC) colonies remain viable long after a water source has been removed, and the MTM produced by SC remain toxic over extended periods of time. We next showed that PC when inhaled, can release in vivo, a protease allergen that can cause a significant allergic inflammatory reaction in the lungs of mice. We then showed, in a laboratory study, that the MTM of SC can become airborne attached to spores or SC particulates smaller than spores. Following that study, we next showed that the same phenomenon actually occurred in SC infested buildings where people were complaining of health problems potentially associated with SBS. Finally, we were able to demonstrate the presence of MTM in the sera of individuals who had been exposed to SC in indoor environments. This last study was done with enough mold exposed individuals to allow for the statistical significance of SC exposure to be evaluated.
Biodegradable Adhesives Composed of Human Serum Albumin and Organic Acid-based Crosslinkers with Active Ester Groups
Authors: Taguchi Tetsushi , Saito Hirofumi , Iwasashi Masashi , Sakane Masataka , Ochiai Naoyuki
Published: October 2009

The organic acid-based crosslinkers trisuccinimidyl citrate (TSC), disuccinimidyl malate (DSM), and disuccinimidyl tartarate (DST) were combined with human serum albumin (HSA) to produce biodegradable solid— liquid-type adhesives, TSC-A, DSM-A, and DST-A. The bonding time of TSC-A, DSM-A, and DST-A was 15, 10, and 5 min, respectively, when the content of organic acid-based crosslinkers was 0.5 mmol and the HSA concentration was 44 w/v%. Five minutes after application of the adhesives, the DST-A adhesive had the greatest bonding strength (489.14 ± 93.06 kPa) compared with TSC-A (120.86 ± 73.83 kPa) and DSM-A (224.44 ± 79.53 kPa). The bonding strength of DSM-A and DST-A increased with increasing DSM or DST content up to 0.5 mmol, after that the bonding strength decreased. While, the bonding strength of the TSC-A adhesive was relatively low at any TSC content compared with the other adhesives. The bonding strength of DST-A with 0.3 mmol of DST increased with increasing HSA concentration up to 44 w/v%, and then decreased. The bonding strength of the DST-A adhesive was 3.2-fold greater than that of a commercial aldehyde-based adhesive and 6-fold greater than that of a fibrin-based adhesive. DST-A has excellent biocompatibility, bioabsorbability, and only mild tissue reaction in rat subcutaneous tissues.
Leadership in Public Sector Partnerships
Authors: Dudau Adina
Published: October 2009

In the complex cobweb of public sector organizational structures, the need to tackle intricate societal problems set the context for a new direction in leadership studies, one that enables the achievement of policy goals by creating collaborative capabilities. In the policy area of children and young people, Local Safeguarding Children Boards (LSCBs) can allow leadership to manifest itself through a number of media. First, the local authority is the statutory designated leader of this partnership in the local community. Second, the representatives of agencies with a duty to cooperate on children’s issues are themselves leaders of their organizations’ resources and commitment to the partnership’s goal. Third, in the light of unprecedented complexity in policy making, getting things done often depends on the leadership capabilities of people and of organizations to work with the tension between multiple sets of professional, organizational and sectoral values. Although, in theory, leadership should be an important element of inter-agency working, essentially being about making things happen beyond usual institutional constraints, in reality however, empirical findings have shown that leadership in LSCBs is systematically inhibited, hence endangering the outcomes of collaborative, inter-professional and inter-organizational work. The article concludes with the paradox of public servants demonstrating leadership in inter-organizational settings while remaining an impersonal administrator subjected to tight public scrutiny. The article seeks to make a contribution to the public policy and management field in general and to that of collaborative management in particular. To this end, the existing developments in the leadership literature have been used to shed light on one case study of one of the more controversial partnerships in the British public sector: LSCBs.
Frank Stacey Memorial Lecture 2008: Scenes from the Departmental Court
Authors: Rhodes R.A.W.
Published: October 2009

This article argues for research grounded in interpretive theory, or the beliefs and practices of actors, and observational fieldwork, or thick descriptions of what the actors think they are doing. However, discussions of theory and method only come to life when they are grounded in fieldwork. So, at the heart of the article is an account of the Private Offices of British central government departments. I argue that the focus on beliefs and practices enables me to tell a new story. The existing literature does not explore how the individuals who comprise the department’s core executive coordinate the department’s tasks and resolve conflicts. There is a ‘departmental court’ that dare not speak its name. By describing the court ‘at work’, I focus not on individual Private Offices but on the tasks of coordination and conflict resolution at the top of the department. I conclude that any approach that provides new evidence and a novel interpretation makes a strong case for inclusion in the armoury of every student of public administration.
The response of a jack pine forest to late-Holocene climate variability in northwestern Wisconsin
Authors: Tweiten Michael A. , Hotchkiss Sara C. , Booth Robert K. , Calcote Randy R. , Lynch Elizabeth A.
Published: October 2009

Terrestrial plant communities have the potential to respond to climate change rapidly, if dominant species are killed by a series of extreme events, or slowly, if the cumulative effects of shorter-term climate fluctuations result in long-term compositional change. We used pollen and charcoal records from a lake and a testate amoebae-derived history of water-table depth in a nearby peatland to assess the response of the jack pine-dominated forests of northwestern Wisconsin to the climate variability of the last ~2000 years. The hydrology record and the charcoal record indicate that the climate near Warner Lake over the last ~2000 years was characterized by multidecadal variation in moisture availability with no apparent multicentennial-long trends in moisture balance or fire frequency. However, the pollen record suggests that there were multicentennial-scale changes in the vegetation composition around Warner Lake. Direct comparison of the three proxy records is challenging, because of their differing temporal resolutions and the complexity of potential ecological responses to climate variability. Therefore, we developed an interpretive model to compare multiple simulated proxies under two scenarios of environmental variability in order to determine under what conditions apparently contradictory records are likely to be found. The interpretive model reveals that a record of multicentennial-long change in vegetation is possible if multidecadal climate variability interacts with ecological processes influencing the direction and magnitude of succession. Compositional changes in the Warner Lake pollen record could reflect long-term variation in temperature, seasonality or other climate factors independent of moisture balance; however it is also possible that multidecadal moisture variability interacted with ecological processes affecting recruitment and mortality of species following fires of varying size and severity. Decadal-scale climatic variability can lead to altered successional pathways and to changes in forest composition that last for centuries.
The lupus susceptibility locus Sle3 is not sufficient to accelerate atherosclerosis in lupus-susceptible low density lipoprotein receptor-deficient mice
Authors: Wade NS , Stevenson BG , Dunlap DS , Major AS
Published: October 2009

Cardiovascular disease risk is increased in individuals suffering from systemic lupus erythematosus. Understanding the mechanism(s) of systemic lupus erythematosus-accelerated atherosclerosis is critical for the development of effective therapies. Our laboratory previously demonstrated that radiation chimeras of systemic lupus erythematosus-susceptible B6.Sle1.2.3 and low density lipoprotein receptor (LDLr)—/— mice have augmented atherosclerosis, which is associated with increased T-cell burden and activation in the lesion. The goals of this study were to further define specific immune mechanisms that mediate accelerated atherosclerosis and to determine whether the gene interval Sle3, which is linked to lupus-associated T-cell dysregulation, was sufficient to modulate atherogenesis. We transferred B6.Sle3 or C57Bl/6-derived bone marrow cells into lethally irradiated LDLr —/— mice (hereafter referred to as LDLr.Sle3 and LDLr.B6, respectively). Sixteen weeks after transplantation, the mice were placed on a western-type diet for 8 weeks. Our analyses revealed that LDLr.Sle3 mice had increased auto-antibody production against double-stranded DNA and cardiolipin compared with LDLr.B6 controls. We also found an increase in atherosclerosis-associated oxLDL antibodies. Antibody isotypes and serum cytokine analysis suggested that the humoral immune response in LDLr.Sle3 mice was skewed toward a Th2 phenotype. This finding is consistent with lupus-associated immune dysregulation. Additionally, LDLr.Sle3 mice had decreased serum cholesterol and triglyceride levels. However, there was no difference in lesion area or cellular composition of lesions between the two groups. These data demonstrate that, despite no change in lesion area, transfer of Sle3-associated T-cell dysregulation alone to LDLr-deficient mice is sufficient to decrease serum cholesterol and to exacerbate humoral immune responses that are frequently associated with atherosclerosis. Lupus (2010) 19, 34—42.
Unsteady Fluid Flow in Hybrid Hydraulic Actuators
Authors: John Shaju , Chaudhuri Anirban , Cadou Christopher , Wereley Norman M.
Published: October 2009

The ability of smart materials like piezoelectrics to deliver large blocking forces in a small package while operating at high frequencies makes them extremely attractive for converting electrical energy to mechanical power. This led to the development of hybrid actuators consisting of co-located smart material actuated pumps and hydraulic cylinders that are connected by a set of fast-acting valves. The overall success of the hybrid concept hinges on the effectiveness of the coupling between the smart material and the fluid. This, in turn, is strongly dependent on the resistance to fluid flow in the device. This article presents results from 3D simulations of unsteady fluid flow in the pumping chamber of a prototype hybrid actuator powered by a piezoelectric stack. The results show that the forces associated with moving the fluid into and out of the pumping chamber exceed 10% of the piezo stack blocked force at relatively low frequencies near 100 Hz and approach 80% of the blocked force at 800 Hz. This reduces the amplitude of the piston motion in such a way that the volume flow rate remains approximately constant above operating frequencies of 600 Hz. As the driving frequency is increased beyond 800 Hz, the flow rate starts to decrease. This study also presents a decomposition of the pressure loss into its Fourier components and identifies the important harmonics.
Coil-based Electromagnetic Damper and Actuator for Vibration Suppression of Cantilever Beams
Authors: Cheng Tai-Hong , Oh Il-Kwon
Published: October 2009

In this study, both an eddy current coil damper and an electromagnetic actuator were developed for the vibration suppression of a cantilever beam integrated with a copper coil and a permanent magnet. The control system for the vibration suppression of the electro-magneto-mechanically coupled beam that consists of a coil attached to an aluminum beam and a permanent magnet installed below the coil was proposed. Alternatively, the conductive coil can be passively and actively used as a damper and an actuator. The effects of various coil shapes including a cylindrical tube, a square tube and a circular sheet were investigated to determine optimal vibration suppression for the cantilever beam. The frequency response function of a beam with the theoretical model of the magnetic eddy current damping system was predicted and its accuracy was compared to the experimentally measured frequency response. Also, the results of the active control with a positive position feedback method were compared with those of the passive eddy current dampers with open and closed circuits. The experimental data showed that the tube type coils had much higher vibration suppression efficiency than the sheet type coil and the active vibration control strategy can be alternatively used to improve the electromagnetic damper system.
Can Neuroscience Help Us Do a Better Job of Teaching Music?
Authors: Hodges Donald A.
Published: October 2009

We are just at the beginning stages of applying neuroscientific findings to music teaching. A simple model of the learning cycle based on neuroscience is Sense → Integrate → Act (sometimes modified as Act → Sense → Integrate). Additional components can be added to the model, including such concepts as active rather than passive learning, learning activates reward centers, all learning is emotionally colored, plasticity, neural pruning, nature and nurture, critical and optimal periods, the pattern-detecting brain, imitation and the social learning brain, group learning, empathy and social emotions, learning is multisensory, and learning requires memory. When this model and the components are applied to music teaching, they confirm best practices. Innovation pedagogical strategies will be forthcoming when there is a better understanding of the brain and music learning.
Feasibility and Acceptability of a School-Based Coping Intervention for Latina Adolescents
Authors: Garcia Carolyn , Pintor Jessie Kemmick , Lindgren Sandi
Published: October 2009

Latino girls (Latinas) experience disproportionate rates of emotional distress, including suicidal ideation, which may be indicative of inadequate coping abilities. Prevention of mental health problems, a U.S. public health priority, is particularly critical for Latina adolescents due to lack of access to mental health treatments. The purpose of this study was to examine the feasibility of Project Wings, a 14-session stress management/coping intervention. Latinas in school (ages 15−21) met weekly for 2-hr with two bilingual experienced facilitators to participate in sharing circles, relaxation exercise, and skill building. Intervention participation and post-intervention focus group data were analyzed. Fall semester intervention ( n = 10) occurred during school (72% attendance rate); spring semester intervention ( n = 11) was after school (84% attendance rate). Focus group data confirmed acceptability. Latina adolescents will participate in a school-based, group-based stress management/coping intervention. The findings offer insights about intervention recruitment and retention that are specifically relevant to school nurses. Future research includes intervention testing using a randomized study design.
Relative Purity of Different Bovine Thrombin Preparations
Authors: Zhu He , Hoppensteadt Debra , Iqbal Omer , Litinas Evangelos , Adiguzel Cafer , Fareed Jawed
Published: October 2009

The aim of this study was to compare the relative purity of bovine crude thrombin and its purified forms, namely, thrombin 4A and thrombin 4B (the products of King Pharma, Middleton, Wisconsin) by virtue of the detection of bovine prothrombin-related antigens in these preparations. Bovine prothrombin was administered intravenously to 3 individual rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic method. Blood was drawn from each rabbit on days 30, 50, 105, 137, and 165, and the pooled antisera from 3 rabbits were purified to isolate immunoglobulin G (IgG) using protein G affinity columns. Using Western blotting method, serially diluted bovine crude thrombin, thrombin 4A, and 4B preparations were probed using the prothrombin IgGs obtained from each time point to explore prothrombin-related antigens in these preparations. The results revealed that compared with the prothrombin IgG collected on day 30, the IgGs collected on days 50 to 165 showed a time-dependent increase in their ability to detect the prothrombin-related antigens in 3 bovine thrombin preparations studied. The lowest amount of crude thrombin, thrombin 4A, and 4B preparations that prothrombin IgG could detect was 0.125, 10, and 20 U, respectively. The rank order of the number of immunoreactive bands detectable in 3 bovine thrombin preparations probed by the prothrombin IgGs collected from any given time point was always the same: crude thrombin > thrombin 4A > thrombin 4B. The results indicate that thrombin 4B preparation contains the least amount of antigens detectable by prothrombin IgG, suggesting that relatively thrombin 4B represents the most purified thrombin preparation among the 3 thrombin preparations studied.
ZEITMOP Concept — A Polygeneration System for Municipal Energy Demands
Authors: Gorski Jan , Yantovski Eugene
Published: October 2009

The reduction of greenhouse gases (to which CO2 contributes over 60%) to stop global warming is now a major priority for governments around the world. One approach, described in this paper, concerns the ‘‘clean energy’’ or ‘‘zero-emission’’ technologies. An original concept of a semi-closed zero emission ion transport membrane oxygen power (ZEITMOP) cycle is being developed. It can be compared to other research initiatives such as clean energy systems and zero-emission natural gas, as a response to the well-recognised challenges. As an answer to the crucial question of reduction of greenhouse gas emissions we propose new zero-emission fuel-fired power plants and boiler houses (‘‘ZEITMOP Boiler & Air Cooler’’ and ‘‘Zero Emission Membrane Smokeless Heating’’). Zero-emission co-generation of power and heat allows such plants to be located in densely populated areas close to the consumer.
International institutions
Authors: Socher Karl
Published: October 2009

Austrian Economics tries to minimize the role of the state. International institutions, like the International Monetary Fund (IMF) and the World Bank (WB), seen under this perspective, often try to fulfil functions of states which are not necessary, for instance, fixing exchange rates or redistribute income. They should concentrate on correcting market failures, like international public goods, when they cannot be supplied by the market, or internalize externalities. But even in these cases, state failures have to be avoided. Such state failures happened especially in countries transforming from socialist to market economies and in advising these states by international institutions.
Travelling vulnerabilities: mobile timespaces of quiescence
Authors: Bissell David
Published: October 2009

This paper investigates the relationship between mobility and embodied experiences of quiescence. Rather than conceptualizing quiescence as an experience that is opposite to activity, this paper explores how various experiences of quiescence emerge through the course of a railway journey. The first section of the paper illustrates how particular dispositions of vulnerability have the potential to generate a series of desirable quiescent experiences such as daydreaming and relaxation. The second section explores how these vulnerable dispositions also have the potential to generate a series of less-comfortable quiescent experiences such as lethargy, tiredness and agitation. In doing so, this paper emphasizes the necessity to take seriously how the experience of travel itself impacts on and conditions the affective capacities of the travelling body for feeling in particular ways. In contrast to work within cultural geography that has focused on the conscious, reflective and signifying practices of the body, this paper illuminates how the multiplicity of quotidian quiescent experiences induces a different set of experiential relationships between a more vulnerable body and the timespace of the railway journey.
Screening Patients in Busy Hospital-Based HIV Care Centers for Hazardous and Harmful Drinking Patterns: The Identification of an Optimal Screening Tool
Authors: Strauss Shiela M. , Rindskopf David M.
Published: October 2009

Because many HIV care providers fail to detect patients’ hazardous drinking, we examined the potential use of the AUDIT-C, the first 3 of the 10 items comprising the Alcohol Use Disorders Identification Test (AUDIT), to efficiently screen patients for alcohol abuse. To perform this examination, we used Item Response Theory (IRT) involving individual AUDIT items and AUDIT instruments completed by patients (N = 400) at a Designated AIDS Center (DAC) in New York City. At various AUDIT-C cutoff scores, specificities and sensitivities were then examined using the AUDIT as a ‘‘gold standard.’’ For cutoff scores on the AUDIT from 4 to 8, cutoff scores on the AUDIT-C of 3 and 4, respectively, resulted in sensitivities between .94-.98 and .81-.89, respectively, and specificities between .82-.91 and .91-1.0, respectively. In busy HIV care centers, the AUDIT-C with cutoff scores of 3 or 4 is a reasonable alternative to the full AUDIT as an alcohol screening instrument.
The Influence of Education and Exercise on Neck Pain
Authors: Hanney William J. , Kolber Morey J. , Schack-Dugre' Judi , Negrete Rodney , Pabian Patrick
Published: October 2009

Neck pain is a significant contributor to worldwide disability and poses a considerable financial burden to its stakeholders. The prognosis for chronic neck pain is generally poor, and the associated disability seems to be more persistent than low back pain. It has been suggested that the goals of a rehabilitation program are to maximize return to function, limit progression of degenerative changes, and prevent further injury. The variety of treatment options can make it difficult for clinicians to agree on the most effective treatment intervention. This article reviews noninvasive treatment considerations for patients with neck pain. Exercise-based interventions, including aerobic conditioning, stretching, and strengthening, are addressed. Moreover, concepts related to education are covered, including the effects of posture and ergonomic counseling.
Leading Small Scottish Primary Schools
Authors: Wilson Valerie
Published: October 2009

Between 1996 and 1998, research commissioned by the Scottish Office Education Department was undertaken on the management of small Scottish primary schools, the results of which were published in this journal (Wilson and McPake, 1998). This article reports the findings from a follow-up study of a sample of 100 schools that participated in the original study (Wilson, 2007). The aim was to explore whether the leadership and management styles of small school headteachers had changed in the intervening years. The research is based upon a postal survey of 100 headteachers of very small schools, i.e. those with rolls of fewer than 50 pupils, in 10 local authorities in Scotland, and also nine case studies. The researcher argues that although the style demonstrated by these headteachers is largely a contingent one that is appropriate to their situations as teaching headteacher s, the pressures on them have increased in the intervening years. Questions regarding the sustainability of the role are raised.
Quasi-regulation and Principal—Agent Relationships
Authors: West Anne , Pennell Hazel , Hind Audrey
Published: October 2009

Market-oriented reforms and school choice policies have had a high political profile in a number of developed countries. This article examines the issue of school choice through the lens of the English market-oriented reforms; it focuses on the quasi-regulation and regulation of admissions to publicly funded secondary schools. It examines admissions to state-maintained secondary schools in London in terms of the criteria and practices used in the event of there being more applicants than places available. It also explores changes in admissions criteria and practices between 2001 and 2005 given the legislative and policy changes introduced in the intervening period. Principal—agent theory is used heuristically to explain the differing responses of schools with responsibility for admissions and local authorities to the legislative and policy framework. It is argued that while local authorities act broadly in line with government guidance and regulations as the agent of the government, schools acting as agents do not necessarily do so and more appear to select particular groups of children as opposed to others. This, it is argued, is because the regulatory mechanisms have been insufficient to motivate them to act as intended in relation to their admissions policies and practices in the light of the other policy goals and incentives accompanying the market-oriented reforms.
Comprehensive genomic screens identify a role for PLZF-RARα as a positive regulator of cell proliferation via direct regulation of c-MYC
Authors: Rice Kim L. , Hormaeche Itsaso , Doulatov Sergei , Flatow Jared M. , Grimwade David , Mills Ken I. , Leiva Magdalena , Ablain Julien , Ambardekar Charuta , McConnell Melanie J. , Dick John E. , Licht Jonathan D.
Published: October 2009

The t(11;17)(q23;q21) translocation is associated with a retinoic acid (RA)–insensitive form of acute promyelocytic leukemia (APL), involving the production of reciprocal fusion proteins, promyelocytic leukemia zinc finger–retinoic acid receptor α (PLZF-RARα) and RARα-PLZF. Using a combination of chromatin immunoprecipitation promotor arrays (ChIP-chip) and gene expression profiling, we identify novel, direct target genes of PLZF-RARα that tend to be repressed in APL compared with other myeloid leukemias, supporting the role of PLZF-RARα as an aberrant repressor in APL. In primary murine hematopoietic progenitors, PLZF-RARα promotes cell growth, and represses Dusp6 and Cdkn2d, while inducing c-Myc expression, consistent with its role in leukemogenesis. PLZF-RARα binds to a region of the c-MYC promoter overlapping a functional PLZF site and antagonizes PLZF-mediated repression, suggesting that PLZF-RARα may act as a dominant-negative version of PLZF by affecting the regulation of shared targets. RA induced the differentiation of PLZF-RARα–transformed murine hematopoietic cells and reduced the frequency of clonogenic progenitors, concomitant with c-Myc down-regulation. Surviving RA-treated cells retained the ability to be replated and this was associated with sustained c-Myc expression and repression of Dusp6, suggesting a role for these genes in maintaining a self-renewal pathway triggered by PLZF-RARα.
MicroRNA 29b functions in acute myeloid leukemia
Authors: Garzon Ramiro , Heaphy Catherine E. A. , Havelange Violaine , Fabbri Muller , Volinia Stefano , Tsao Twee , Zanesi Nicola , Kornblau Steven M. , Marcucci Guido , Calin George A. , Andreeff Michael , Croce Carlo M.
Published: October 2009

MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of acute myelogeneous leukemia (AML), but their impact on AML pathogenesis is poorly understood. We have previously shown that miR-29b expression is deregulated in primary AML blasts. In this work, we investigated the functional role of miR-29b in leukemogenesis. Restoration of miR-29b in AML cell lines and primary samples induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia model. Transcriptome analysis after ectopic transfection of synthetic miR-29b into leukemia cells indicates that miR-29b target apoptosis, cell cycle, and proliferation pathways. A significant enrichment for apoptosis genes, including MCL-1, was found among the mRNAs inversely correlated with miR-29b expression in 45 primary AML samples. Together, the data support a tumor suppressor role for miR-29 and provide a rationale for the use of synthetic miR-29b oligonucleotides as a novel strategy to improve treatment response in AML.
How I treat CLL up front
Authors: Gribben John G.
Published: October 2009

Although chronic lymphocytic leukemia (CLL) remains incurable, over the past decade there have been major advances in understanding the pathophysiology of CLL and in the treatment of this disease. This has led to greatly increased response rates and durations of response but not yet improved survival. Advances in the use of prognostic factors that identify patients at high risk for progression have led us to the question whether there is still a role for a “watch and wait” approach in asymptomatic high-risk patients or whether they should be treated earlier in their disease course. Questions remain, including, what is the optimal first-line treatment and its timing and is there any role of maintenance therapy or stem cell transplantation in this disease? CLL is a disease of the elderly and not all patients are eligible for aggressive up-front chemoimmunotherapy regimens, so what is the optimal treatment approach for more frail elderly patients? It is highly likely that our treatment approaches will continue to evolve as the results of ongoing clinical trials are released and that further improvements in the outcome of this disease will result from identification of therapies that target the underlying pathophysiology of CLL.
Nme protein family evolutionary history, a vertebrate perspective
Authors: Desvignes Thomas , Pontarotti Pierre , Fauvel Christian , Bobe Julien
Published: October 2009

Background

The Nme family, previously known as Nm23 or NDPK, is involved in various molecular processes including tumor metastasis and some members of the family, but not all, exhibit a Nucleoside Diphosphate Kinase (NDPK) activity. Ten genes are known in humans, in which some members have been extensively studied. In non-mammalian species, the Nme protein family has received, in contrast, far less attention. The picture of the vertebrate Nme family remains thus incomplete and orthology relationships with mammalian counterparts were only partially characterized. The present study therefore aimed at characterizing the Nme gene repertoire in vertebrates with special interest for teleosts, and providing a comprehensive overview of the Nme gene family evolutionary history in vertebrates.

Results

In the present study, we present the evolutionary history of the Nme family in vertebrates and characterize the gene family repertoire for the first time in several non-mammalian species. Our observations show that vertebrate Nme genes can be separated in two evolutionary distinct groups. Nme1, Nme2, Nme3, and Nme4 belong to Group I while vertebrate Nme5, Nme6, Nme7, Nme8, and Nme9 belong to Group II. The position of Nme10 is in contrast more debatable due to its very specific evolutionary history. The present study clearly indicates that Nme5, Nme6, Nme7, and Nme8 originate from duplication events that occurred before the chordate radiation. In contrast, Nme genes of the Group I have a very different evolutionary history as our results suggest that they all arise from a common gene present in the chordate ancestor. In addition, expression patterns of all zebrafish nme transcripts were studied in a broad range of tissues by quantitative PCR and discussed in the light of the function of their mammalian counterparts.

Conclusion

This work offers an evolutionary framework that will pave the way for future studies on vertebrate Nme proteins and provides a unified vertebrate Nme nomenclature that is consistent with the nomenclature in use in mammals. Based on protein structure and expression data, we also provide new insight into molecular functions of Nme proteins among vertebrates and raise intriguing questions on the roles of Nme proteins in gonads.
Acute sensorineural hearing loss and severe otalgia due to scrub typhus
Authors: Kang Ji-In , Kim Dong-Min , Lee Joonhan
Published: October 2009

Background

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi.

Case presentations

We encountered a patient with sensorineural hearing loss complicating scrub typhus, and three patients with scrub typhus who complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent yet persistent pain lasting for several seconds, appeared within 1 week after the onset of fever and rash. The acute sensorineural hearing loss and otalgia were resolved after antibiotic administration.

Conclusion

When patients in endemic areas present with fever and rash and have sensorineural hearing loss or otalgia without otoscopic abnormalities, clinicians should suspect scrub typhus and consider empirical antibiotic therapy.
Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer
Authors: Merritt Melissa A , Parsons Peter G , Newton Tanya R , Martyn Adam C , Webb Penelope M , Green Adèle C , Papadimos David J , Boyle Glen M
Published: October 2009

Background

The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression.

Methods

Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes.

Results

We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity.

Conclusion

These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis.
Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells
Authors: Cervera Ana M , Bayley Jean-Pierre , Devilee Peter , McCreath Kenneth J
Published: October 2009

Remodelling of mitochondrial metabolism is a hallmark of cancer. Mutations in the genes encoding succinate dehydrogenase (SDH), a key Krebs cycle component, are associated with hereditary predisposition to pheochromocytoma and paraganglioma, through mechanisms which are largely unknown. Recently, the jumonji-domain histone demethylases have emerged as a novel family of 2-oxoglutarate-dependent chromatin modifiers with credible functions in tumourigenesis. Using pharmacological and siRNA methodologies we show that increased methylation of histone H3 is a general consequence of SDH loss-of-function in cultured mammalian cells and can be reversed by overexpression of the JMJD3 histone demethylase. ChIP analysis revealed that the core promoter of IGFBP7, which encodes a secreted protein upregulated after loss of SDHB, showed decreased occupancy by H3K27me3 in the absence of SDH. Finally, we provide the first evidence that the chief (type I) cell is the major methylated histone-immunoreactive constituent of paraganglioma. These results support the notion that loss of mitochondrial function alters epigenetic processes and might provide a signature methylation mark for paraganglioma.
Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design
Authors: Seo Jae-Bin , Jeon Hui-Kyung , Park Kyung-Woo , Park Jong-Seon , Bae Jang-Ho , Kim Sang-Wook , Moon Keon-Woong , Choi Jae-Woong , Lee Sang-Gon , Chung Woo-Young , Youn Tae-Jin , Kim Soo-Joong , Kim Doo-Il , Kim Byung-Ok , Hyon Min-Su , Park Keum-Soo , Cha Tae-Joon , Hwang Hweung-Kon , Hur Seung-Ho , Kim Hyo-Soo
Published: October 2009

Background

Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1st generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.

Methods

In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.

Discussion

The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.

Trial registration

ClinicalTrials.gov number, NCT00699543.
AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis
Authors: Zerp Shuraila F , Stoter Rianne , Kuipers Gitta , Yang Dajun , Lippman Marc E , van Blitterswijk Wim J , Bartelink Harry , Rooswinkel Rogier , Lafleur Vincent , Verheij Marcel
Published: October 2009

Background

Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity bothin vitroandin vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies.

Methods

We tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XLis known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach.

Results

AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced.

Conclusion

Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination therapies.
Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites
Authors: Brolin Kim JM , Ribacke Ulf , Nilsson Sandra , Ankarklev Johan , Moll Kirsten , Wahlgren Mats , Chen Qijun
Published: October 2009

Background

Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology.

Results

We demonstrate an approach combining real-time PCR allelic discrimination and discriminative RNA-FISH to distinguish between highly similar gene copies in P. falciparum parasites. The duplicated var2csa variants are simultaneously transcribed, both on a population level and intriguingly also in individual cells, with nuclear co-localization of the active genes and corresponding transcripts. This indicates transcriptional functionality of duplicated genes, challenges the dogma of mutually exclusive var gene transcription and suggests mechanisms behind antigenic variation, at least in respect to the duplicated and highly similar var2csa genes.

Conclusions

Allelic discrimination assays have traditionally been applied to study zygosity in diploid genomes. The assays presented here are instead successfully applied to the identification and evaluation of transcriptional activity of duplicated genes in the haploid genome of the P. falciparum parasite. Allelic discrimination and gene or transcript localization by FISH not only provide insights into transcriptional regulation of genes such as the virulence associated var genes, but also suggest that this sensitive and precise approach could be used for further investigation of genome dynamics and gene regulation.
Reduced transcript stabilization restricts TNF-α expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan
Authors: Basler Tina , Holtmann Helmut , Abel Jens , Eckstein Torsten , Bäumer Wolfgang , Valentin-Weigand Peter , Goethe Ralph
Published: October 2009

Lack of p38 MAPK-dependent TNF-α mRNA stabilization in Mycobacterium avium ssp. paratuberculosis-infected macrophages.

Despite the critical role that TNF-α plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn’s disease. We found that in MAP-infected macrophages, TNF-α gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF-α transcription alone could not fully explain the differential TNF-α mRNA expression, suggesting that there must be a substantial contribution by post-transcriptional mechanisms. Accordingly, we found reduced TNF-α mRNA stability in MAP-infected macrophages. Further comparison of MAP- and MS-infected macrophages revealed that lower TNF-α mRNA stability combined with lower mRNA and protein expression in MAP-infected macrophages correlated with lower p38 MAPK phosphorylation. Theses findings were independent of viability of MAP and MS. We demonstrate that the major mycobacterial cell-wall lipoglycan LM of MAP and MS induced TNF-α mRNA transcription, but only the MS-LM induced p38 MAPK-dependent transcript stabilization. Overall, our data suggest that pathogenic mycobacteria cause weak p38 MAPK activation and TNF-α mRNA stabilization as a result of their structural cell-wall components such as LM and thereby, restrict TNF-α expression in macrophages.