bluuebunny/crossref_metadata_2025 huggingface dataset:
Taming the Dalit Panthers
Authors: Gorringe Hugo
Published: June 2007

Although Dalit orators and slogans threaten (or promise) to ‘turn Tamil Nadu on its head’, the 2006 state elections offer Dalit analysts pause for thought. In compromising its principles and allying with established parties, the Dalit Panther Iyyakkam (Movement), the largest Dalit movement in the state, has come full circle since 1999. In alternately backing the two dominant parties in the state (the DMK and the AIADMK), the DPI appears to be increasingly institutionalised. Excavating the future of Dalit action from past trends and contemporary politics, I suggest that Dalit parties are following an established political repertoire in which a phase of militant activism gives way to ‘politics as normal’. In the face of this analysis the paper asks whether such an approach is sustainable or can carry the majority of Dalits with it. If Dalit politics is a continuation of hegemonic politics, it argues, the liberatory promises of Dalit activism will have been betrayed.
Guaranteeing Elementary Education
Authors: Jha Praveen
Published: June 2007

This paper attempts to assess contemporary policies/programmes and financial commitments of the Indian state in providing elementary education to its children, as this, arguably, is among the most important basic needs in any society. As is well-known, in spite of the frequent rhetoric to the contrary, there has been a serious neglect in the public provisioning of this need, and the schooling system in India is nowhere near ready to provide a decent quality of education to all its children. Inadequate spending, as well as the malfunctioning of schools and other relevant institutions, have been the obvious bottlenecks constraining India's progress. Ostensibly, there is a greater sense of urgency in contemporary official discourses to address existing problems and move forward rapidly. However, our reading is that public commitment to quality elementary education continues to be half-hearted. The policy initiatives of the government in the last few years do not generate much optimism with respect to addressing the huge deficits in the education sector, and even appear to be retrogressive in important ways
The Rationale of Self-help in Development Interventions
Authors: Jakimow Tanya
Published: June 2007

Self-help is often perceived as a valuable, if not essential, element to development programmes. At the same time, as a concept it has generally escaped scrutiny. Two types of claims are made about the benefits of selfhelp programmes. First, it is suggested that self-help empowers its participants more so than other externally directed or implemented programmes. The second less vocal claim is the compatibility of self-help with cost-reduction strategies: both in terms of material costs and costs to the prevailing social and economic structure. This article explores these two claims through a case study of a self-help group (SHG) programme in Tamil Nadu, India. It argues that although empowering outcomes are stated as the rationale for self-help, these are often neglected in favour of achieving cost-reduction ones. This is an outcome of the concept of self-help being absorbed into the practices and discourses of the dominant development paradigm. Self-help has thus been divorced from its role in enabling self-direction, and has become the rationale for pressuring the marginalised to take responsibility for improving their own condition within a non-negotiable economic and social structure.
Prison officer training and practice in Nigeria
Authors: Jefferson Andrew M.
Published: June 2007

Prisons and prison guards in Africa remain understudied and ill understood and are most often represented in the literature as objects/subjects of critique or targets of reform. To begin to redress this balance, drawing on eight months of ethnographic fieldwork conducted among prison officers in Nigeria, this article examines prison officer training and the penal philosophy and practice of the Nigerian Prisons Service. Documentation of the contradictions of prison training practice reveals how pretensions to discipline, order and hierarchy are challenged both from below and above at the level of everyday practice. What look like hegemonic practices are, not surprisingly, contested and contradictory. Via a partial ethnography of prison training school practice the article presents a challenge to reform agencies seeking to transform penal institutions via methods that assume the homogeneity of the targeted institutions. A suggestion is made that perhaps the contested nature of penal practices in the South may encourage reform agencies to reconfigure their own identities by tapping in to internal contradictions rather than trying to impose change from without. A space for re-imagining reform strategies is framed that takes the potential but inevitable contradictions and ambiguities of prison practice as its reference point.
Narrative and the construction of `truth' in a prison-based treatment program for sexual offenders
Authors: Waldram James B.
Published: June 2007

This article examines the conflict that ensues over the meaning of `truth' in a treatment program for imprisoned sexual offenders. Based on ethnographic research in a prison hospital, extensive interview and observational data are employed to demonstrate the pervasiveness of truth discourse in both treatment and everyday living on the unit. Through the application of a narrative analytic framework, it is argued that the inherent incompatibility between autobiography and disclosure — or narrative and paradigmatic modes of thought, to use Bruner's (1986, 1991) terms — explains how and why inmates struggle to accept the re-emplotment of their life stories demanded by treatment staff.
Understanding Cultural Omnivorousness: Or, the Myth of the Cultural Omnivore
Authors: Warde Alan , Wright David , Gayo-Cal Modesto
Published: June 2007

The concept of omnivorousness has become influential in the sociologies of culture and consumption, cited variously as evidence of altered hierarchies in cultural participation and as indicative of broader socio-cultural changes. The ‘omnivore thesis’ contends that there is a sector of the population of western countries who do and like a greater variety of forms of culture than previously, and that this broad engagement reflects emerging values of tolerance and undermines snobbery. This article draws on the findings of a study of cultural participation in the UK to explore the coherence of the omnivore thesis. It uses a survey to identify and isolate omnivores, and then proceeds to explore the meanings of omnivorousness through the analysis of in-depth, qualitative interviews with them. It concludes that, while there is evidence of wide cultural participation within the UK, the figure of the omnivore is less singularly distinctive than some studies have suggested.
Contesting Ethical Trade in Colombia's Cut-Flower Industry: A Case of Cultural and Economic Injustice
Authors: Wright Caroline , Madrid Gilma
Published: June 2007

Based on a case study of Colombia’s cut-flower industry, this article draws strategically on Nancy Fraser’s model of (in)justice to explore the mutual entwinement of culture and economy. It examines responses by cut-flower employers and their representatives to ethical trade discourses demanding economic justice for Colombia’s largely female cut-flower workers. It argues that employers’ misrecognition of both ethical trade campaigners and cut-flower workers may serve to deny and redefine claims of maldistribution.Through a ‘home-grown’ code of conduct, employers also seek to appropriate ethical trade in their own interests. Finally, a gender coding of worker misrecognition ostensibly displaces workers’ problems from the economic realm to the cultural, offering the ‘modernity’ of full capitalist relations as the solution. In further examining the ‘responses to the responses’ by workers and their advocates, the contestation of ethical trade is highlighted and its prospects assessed.
Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease
Authors: Ryu Y. J. , Kim E. J. , Lee S-H. , Kim S. Y. , Suh G. Y. , Chung M. P. , Kim H. , Kwon O. J. , Koh W-J.
Published: June 2007

The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such asMycobacterium aviumand lipoteichoic acid (LTA).

Reverse transcriptase–PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-α.

Expression of TLR2 mRNA by peripheral blood monocytes after stimulation withM. aviumor LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-α mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreasedM. avium- and LTA-induced IL-12 p40 and TNF-α production in healthy controls, but not in NTM patients.

The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-α followingMycobacterium aviumor lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.
Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnoea patients
Authors: Oliven A. , Tov N. , Geitini L. , Steinfeld U. , Oliven R. , Schwartz A. R. , Odeh M.
Published: June 2007

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion.

The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation.

Genioglossus contraction decreased the critical pressure significantly from 1.2±3.3 to -0.7±3.8 cmH2O, with individual decreases ranging -0.6–5.9 cmH2O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx.

Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.
Factors determining early adherence to a lung cancer screening protocol
Authors: Montes U. , Seijo L. M. , Campo A. , Alcaide A. B. , Bastarrika G. , Zulueta J. J.
Published: June 2007

Lung cancer screening using computed tomography (CT) is effective in detecting early stage disease. However, concerns regarding adherence have been raised.

The current authors conducted a retrospective observational study of 641 asymptomatic smokers enrolled in a lung cancer screening programme between 2000 and 2003. Adherent subjects were compared with nonadherent subjects with regard to lung function, sex, age, motivation for enrolment, smoking status, distance to the referral centre, family history of lung cancer, asbestos exposure, education, the presence and type of nodule(s) seen on initial CT, and exposure to a nursing intervention designed to improve adherence.

Overall, early adherence to the study protocol was 65%. Multivariate analysis confirmed the importance of sex, proximity to the referral centre, the presence of noncalcified nodules, and the nursing intervention as factors conditioning adherence to the study protocol. Patients encouraged to participate in the study were more adherent, as were former smokers. Sex interactions were observed in multivariate analysis. The nursing intervention was significant for females, while abnormal lung function improved male adherence.

Adherence to lung cancer screening is particularly good among females and subjects living near the referral centre. The present study suggests the need to develop new strategies, especially those targeting males and subjects with low risk perception, in order to improve adherence.
A Three Stage Integrative Pathway Search (TIPS©) framework to identify toxicity relevant genes and pathways
Authors: Li Zheng , Srivastava Shireesh , Mittal Sheenu , Yang Xuerui , Sheng Lufang , Chan Christina
Published: June 2007

Background

The ability to obtain profiles of gene expressions, proteins and metabolites with the advent of high throughput technologies has advanced the study of pathway and network reconstruction. Genome-wide network reconstruction requires either interaction measurements or large amount of perturbation data, often not available for mammalian cell systems. To overcome these shortcomings, we developed a Three Stage Integrative Pathway Search (TIPS
©) approach to reconstruct context-specific active pathways involved in conferring a specific phenotype, from limited amount of perturbation data. The approach was tested on human liver cells to identify pathways that confer cytotoxicity.

Results

This paper presents a systems approach that integrates gene expression and cytotoxicity profiles to identify a network of pathways involved in free fatty acid (FFA) and tumor necrosis factor-α (TNF-α) induced cytotoxicity in human hepatoblastoma cells (HepG2/C3A). Cytotoxicity relevant genes were first identified and then used to reconstruct a network using Bayesian network (BN) analysis. BN inference was used subsequently to predict the effects of perturbing a gene on the other genes in the network and on the cytotoxicity. These predictions were subsequently confirmed through the published literature and further experiments.

Conclusion

The TIPS
© approach is able to reconstruct active pathways that confer a particular phenotype by integrating gene expression and phenotypic profiles. A web-based version of TIPS
© that performs the analysis described herein can be accessed at http://www.egr.msu.edu/tips.
Using expression arrays for copy number detection: an example from E. coli
Authors: Skvortsov Dmitriy , Abdueva Diana , Stitzer Michael E , Finkel Steven E , Tavaré Simon
Published: June 2007

Background

The sequencing of many genomes and tiling arrays consisting of millions of DNA segments spanning entire genomes have made high-resolution copy number analysis possible. Microarray-based comparative genomic hybridization (array CGH) has enabled the high-resolution detection of DNA copy number aberrations. While many of the methods and algorithms developed for the analysis microarrays have focused on expression analysis, the same technology can be used to detect genetic alterations, using for example standard commercial Affymetrix arrays. Due to the nature of the resultant data, standard techniques for processing GeneChip expression experiments are inapplicable.

Results

We have developed a robust and flexible methodology for high-resolution analysis of DNA copy number of whole genomes, using Affymetrix high-density expression oligonucleotide microarrays. Copy number is obtained from fluorescence signals after processing with novel normalization, spatial artifact correction, data transformation and deletion/duplication detection. We applied our approach to identify deleted and amplified regions in E. coli mutants obtained after prolonged starvation.

Conclusion

The availability of Affymetrix expression chips for a wide variety of organisms makes the proposed array CGH methodology useful more generally.
Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor
Authors: Joshi Saurabh , Davies Holly , Sims Lauren Porter , Levy Shawn E , Dean Jurrien
Published: June 2007

Background

Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (FactorIn theGermLine,Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes.

Results

Taking advantage ofFiglanull mouse lines, we have used a combined approach of microarray andSerialAnalysis ofGeneExpression (SAGE) to identify potential downstream target genes. Using high stringent cutoffs, we find that FIGLA functions as a key regulatory molecule in coordinating expression of the NALP family of genes, genes of known oocyte-specific expression and a set of functionally un-annotated genes. FIGLA also inhibits expression of male germ cell specific genes that might otherwise disrupt normal oogenesis.

Conclusion

These data implicate FIGLA as a central regulator of oocyte-specific genes that play roles in folliculogenesis, fertilization and early development.
Oxygen restriction increases the infective potential of Listeria monocytogenes in vitro in Caco-2 cells and in vivo in guinea pigs
Authors: Bo Andersen Jens , Roldgaard Bent B , Christensen Bjarke Bak , Licht Tine Rask
Published: June 2007

Background

Listeria monocytogenes has been implicated in several food borne outbreaks as well as sporadic cases of disease. Increased understanding of the biology of this organism is important in the prevention of food borne listeriosis.

The infectivity of Listeria monocytogenes ScottA, cultivated with and without oxygen restriction, was compared in vitro and in vivo. Fluorescent protein labels were applied to allow certain identification of Listeria cells from untagged bacteria in in vivo samples, and to distinguish between cells grown under different conditions in mixed infection experiments.

Results

Infection of Caco-2 cells revealed that Listeria cultivated under oxygen-restricted conditions were approximately 100 fold more invasive than similar cultures grown without oxygen restriction. This was observed for exponentially growing bacteria, as well as for stationary-phase cultures.

Oral dosage of guinea pigs with Listeria resulted in a significantly higher prevalence (p < 0.05) of these bacteria in jejunum, liver and spleen four and seven days after challenge, when the bacterial cultures had been grown under oxygen-restricted conditions prior to dosage. Additionally, a 10–100 fold higher concentration of Listeria in fecal samples was observed after dosage with oxygen-restricted bacteria. These differences were seen after challenge with single Listeria cultures, as well as with a mixture of two cultures grown with and without oxygen restriction.

Conclusion

Our results show for the first time that the environmental conditions to which L. monocytogenes is exposed prior to ingestion are decisive for its in vivo infective potential in the gastrointestinal tract after passage of the gastric barrier. This is highly relevant for safety assessment of this organism in food.
Performance of the EQ-5D and the EQ-5D+C in elderly patients with cognitive impairments
Authors: Wolfs Claire AG , Dirksen Carmen D , Kessels Alfons , Willems Daniëlle CM , Verhey Frans RJ , Severens Johan L
Published: June 2007

Background

The EQ-5D is a reliable tool for measuring Health-Related Quality of Life (HRQoL). However, concern has been expressed that it may ignore elements of HRQoL, particularly cognition. In response to this concern, the EQ-5D has been extended with a cognitive dimension (EQ-5D+C). The aim of this study was to compare the performance of the EQ-5D and the EQ-5D+C in elderly patients with cognitive impairments by assessing their construct validity and responsiveness.

Methods

Data from the MEDICIE study (n = 196) were used, in which all questionnaires were rated by proxies.

Results

Regarding construct validity, we found similar correlations between the EQ-5D and the Mini Mental State Examination (MMSE) and between the EQ-5D+C and the MMSE. Furthermore, both the EQ-5D and the EQ-5D+C were responsive to changes in the MMSE, with the EQ-5D performing slightly better.

Conclusion

We conclude that the EQ-5D performs well for evaluating HRQoL in a population with cognitive impairments. Based on the results of this explorative study, it does not seem necessary to adjust the current classification system by adding a cognitive dimension. However, in order to compare both instruments regarding utility values, it is necessary to develop a new scoring algorithm for the EQ-5D+C by conducting a general population study. Considering the explorative nature of this study, it is recommended that more aspects of the validity of both the EQ-5D and the EQ-5D+C are explored in patients with cognitive impairments using a more tailored study design.
Use of dynamic microsimulation to predict disease progression in patients with pneumonia-related sepsis
Authors: Saka Görkem , Kreke Jennifer E , Schaefer Andrew J , Chang Chung-Chou H , Roberts Mark S , Angus Derek C ,   the GenIMS Investigators
Published: June 2007

Introduction

Sepsis is the leading cause of death in critically ill patients and often affects individuals with community-acquired pneumonia. To overcome the limitations of earlier mathematical models used to describe sepsis and predict outcomes, we designed an empirically based Monte Carlo model that simulates the progression of sepsis in hospitalized patients over a 30-day period.

Methods

The model simulates changing health over time, as represented by the Sepsis-related Organ Failure Assessment (SOFA) score, as a function of a patient's previous health state and length of hospital stay. We used data from patients enrolled in the GenIMS (Genetic and Inflammatory Markers of Sepsis) study to calibrate the model, and tested the model's ability to predict deaths, discharges, and daily SOFA scores over time using different algorithms to estimate the natural history of sepsis. We evaluated the stability of the methods using bootstrap sampling techniques.

Results

Of the 1,888 patients originally enrolled, most were elderly (mean age 67.77 years) and white (80.72%). About half (47.98%) were female. Most were relatively ill, with a mean Acute Physiology and Chronic Health Evaluation III score of 56 and Pneumonia Severity Index score of 73.5. The model's estimates of the daily pattern of deaths, discharges, and SOFA scores over time were not statistically different from the actual pattern when information about how long patients had been ill was included in the model (P = 0.91 to 0.98 for discharges; P = 0.26 to 0.68 for deaths). However, model estimates of these patterns were different from the actual pattern when the model did not include data on the duration of illness (P < 0.001 for discharges; P = 0.001 to 0.040 for deaths). Model results were stable to bootstrap validation.

Conclusion

An empiric simulation model of sepsis can predict complex longitudinal patterns in the progression of sepsis, most accurately by models that contain data representing both organ-system levels of and duration of illness. This work supports the incorporation into mathematical models of disease of the clinical intuition that the history of disease in an individual matters, and represents an advance over several prior simulation models that assume a constant rate of disease progression.
The impact of cell-bound antigen transport on mucosal tolerance induction
Authors: Pabst Oliver , Bernhardt Günter , Förster Reinhold
Published: June 2007

Mucosal surfaces are exposed continuously to a flood of foreign antigens demanding a tightly controlled balance between immunity and tolerance induction. Tolerance toward food and inhaled antigens, known as oral and respiratory tolerance, respectively, evokes a body-wide nonresponsiveness against the plethora of environmental antigens. Key issues in understanding the induction of mucosal tolerance relate to the site of antigen entrance, the mechanisms of antigen transport, and the exact anatomical location where lymphocytes meet their cognate antigens. In this regard, opposing ideas have been put forward: In one scenario, antigens taken up at mucosal surfaces are considered to spread throughout the body, thus potentially evoking tolerogenic immune responses in all secondary lymphoid organs. Alternatively, tolerance induction might be confined to the draining regional lymph nodes (LN). Recent observations strongly supported the latter scenario, emphasizing the importance of regional LN and their network of afferent lymphatics in this process. In this model, air-borne and intestinal antigens are captured at mucosal sites by dendritic cells, which then migrate exclusively in a CCR7-dependent way to draining regional LN. Tolerance is then induced actively by the activation of antigen-specific T cells, which are subsequently deleted, become anergic, or alternatively, differentiate into regulatory T cells. Thus, the concept of local induction of immune responses seems to hold true for the majority of immune reactions, regardless of whether they are tolerogenic or defensive in their outcome.
Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation
Authors: Mueller Chris G , Boix Charlotte , Kwan Wing-Hong , Daussy Cécile , Fournier Emilie , Fridman Wolf H , Molina Thierry J
Published: June 2007

Large B cell lymphomas can comprise numerous CD14+ cells in the tumor stroma, which raises the question of whether monocytes can support B cell survival and proliferation. We show that the coculture of monocytes with B cells from peripheral blood or from diffuse large B cell lymphoma enabled prolonged B cell survival. Under these conditions, diffuse large lymphoma B cells proliferated, and addition of B cell-activating factor of the TNF family (BAFF) and IL-2 enhanced cell division. Monocytes and dendritic cells (DC) had similar antiapoptotic activity on healthy B cells but displayed differences with respect to B cell proliferation. Monocytes and cord blood-derived CD14+ cells promoted B cell proliferation in the presence of an anti-CD40 stimulus, whereas DC supported B cell proliferation when activated through the BCR. DC and CD14+ cells were able to induce plasmocyte differentiation. When B cells were activated via the BCR or CD40, they released the leukocyte attractant CCL5, and this chemokine is one of the main chemokines expressed in diffuse large B cell lymphoma. The data support the notion that large B cell lymphoma recruit monocytes via CCL5 to support B cell survival and proliferation.
Negative regulation of TLR9-mediated IFN-α induction by a small-molecule, synthetic TLR7 ligand
Authors: Marshall Jason D , Heeke Darren S , Gesner Marianne L , Livingston Brian , Van Nest Gary
Published: June 2007

Toll-like receptors (TLRs) are a family of molecules that function as sensors for the detection of foreign pathogens through the recognition of nonvariable microbial motifs. Although numerous studies have focused on singular TLRs, less attention has been focused on how simultaneous signaling of multiple TLRs may result in counter-regulation of the effects of each. Here, we examine the counter-regulation that occurs during simultaneous stimulation of TLR7 and TLR9 on human plasmacytoid dendritic cels (PDCs) and B cells. Interestingly, we observed that the capacity for potent IFN-α-induction by TLR9 ligands like CpG-C and CpG-A is markedly reduced by concurrent small molecule TLR7 stimulation. However, this inhibition is specific to particular CpG motif-containing immunostimulatory sequence (ISS) functions such as IFN-α induction and BDCA-2 down-regulation. Other ISS activities such as PDC expression of CD80/CD86, secretion of IL-6, and B cell proliferation are not altered by the presence of TLR7 ligands (TLR7Ls). In concordance with the ability of TLR7Ls to decrease IFN-α secretion induced by ISS, we also find that the expression of interferon regulatory factor-7 (IRF-7), a transcriptional factor critical for IFN-α expression, is reduced. Furthermore, down-regulation of TLR9 mRNA expression is accelerated after TLR7 stimulation. These data indicate that TLR7 and TLR9 costimulation do not combine synergistically for IFN-α induction and demonstrate that, instead, a negative feedback mechanism has evolved, possibly to prevent levels of IFN-α secretion potentially detrimental to the host.
Slit-2/Robo-1 modulates the CXCL12/CXCR4-induced chemotaxis of T cells
Authors: Prasad Anil , Qamri Zahida , Wu Jane , Ganju Ramesh K
Published: June 2007

Slit, which mediates its function by binding to the Roundabout (Robo) receptor, has been shown to regulate neuronal, dendritic, and leukocyte migration. However, the molecular mechanism by which the Slit/Robo complex inhibits the migration of cells is not well defined. Here, we showedthat Slit-2 can inhibit the CXCL12-induced chemotaxis and transendothelial migration of T cells and monocytes. We observed that CXCR4 associates with Robo-1 and that Slit-2 treatment enhances this association with the Robo-1 receptor. Robo-1 is a single-pass transmembrane receptor whose intracellular region contains four conserved motifs designated as CC0, CC1, CC2, and CC3. Structural and functional analyses of Robo receptors revealed that interaction of the CC3 motif with the CXCR4 receptor may regulate the CXCL12-induced chemotaxis of T cells. We further characterized Slit-2-mediated inhibition of the CXCL12/CXCR4 chemotactic pathway and found that Slit-2 can block the CXCL12-induced activation of the Src and Lck kinases but not Lyn kinase. Although Slit-2 did not inhibit the CXCL12-induced activation of MAPKs, it did inhibit the Akt phosphorylation and Rac activation induced by this chemokine. Altogether, our studies indicate a novel mechanism by which the Slit/Robo complex may inhibit the CXCR4/CXCL12-mediated chemotaxis of T cells.
Relationship between Bone Mineral Density Changes and Fracture Risk Reduction in Patients Treated with Strontium Ranelate
Authors: Bruyere Olivier , Roux Christian , Detilleux Johann , Slosman Daniel O. , Spector Tim D. , Fardellone Patrice , Brixen Kim , Devogelaer Jean-Pierre , Diaz-Curiel Manuel , Albanese Carlina , Kaufman Jean-Marc , Pors-Nielsen Stig , Reginster Jean-Yves
Published: June 2007

Objective: Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate.

Patients: Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated.

Outcome Measures: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation.

Results: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1–5%) and 2% (1–4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04).

Conclusion: During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.
Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice
Authors: Seki Yoshiyuki , Yamaji Masashi , Yabuta Yukihiro , Sano Mitsue , Shigeta Mayo , Matsui Yasuhisa , Saga Yumiko , Tachibana Makoto , Shinkai Yoichi , Saitou Mitinori
Published: June 2007

We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (H3K9me2),and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re-establishment of potential totipotency in the germline. We here explored a cellular dynamics associated with this epigenetic reprogramming. We found that PGCs undergo erasure of H3K9me2 and upregulation of H3K27me3 in a progressive, cell-by-cell manner, presumably depending on their developmental maturation. Before or concomitant with the onset of H3K9 demethylation, PGCs entered the G2 arrest of the cell cycle, which apparently persisted until they acquired high H3K27me3 levels. Interestingly, PGCs exhibited repression of RNA polymerase II-dependent transcription, which began after the onset of H3K9me2 reduction in the G2 phase and tapered off after the acquisition of high-level H3K27me3. The epigenetic reprogramming and transcriptional quiescence were independent from the function of Nanos3. We found that before H3K9 demethylation, PGCs exclusively repress an essential histone methyltransferase, GLP, without specifically upregulating histone demethylases. We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs.
Binary cell fate specification duringC. elegansembryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivatorβ-catenin SYS-1
Authors: Huang Shuyi , Shetty Premnath , Robertson Scott M. , Lin Rueyling
Published: June 2007

C. elegans embryos exhibit an invariant lineage comprised primarily of a stepwise binary diversification of anterior-posterior (A-P)blastomere identities. This binary cell fate specification requires input from both the Wnt and MAP kinase signaling pathways. The nuclear level of the TCF protein POP-1 is lowered in all posterior cells. We show here that theβ-catenin SYS-1 also exhibits reiterated asymmetry throughout multiple A-P divisions and that this asymmetry is reciprocal to that of POP-1. Furthermore, we show that SYS-1 functions as a coactivator for POP-1, and that the SYS-1-to-POP-1 ratio appears critical for both the anterior and posterior cell fates. A high ratio drives posterior cell fates, whereas a low ratio drives anterior cell fates. We show that the SYS-1 and POP-1 asymmetries are regulated independently, each by a subset of genes in the Wnt/MAP kinase pathways. We propose that two genetic pathways, one increasing SYS-1 and the other decreasing POP-1 levels, robustly elevate the SYS-1-to-POP-1 ratio in the posterior cell, thereby driving A-P differential cell fates.
AtMAP70-5, a divergent member of the MAP70 family of microtubule-associated proteins, is required for anisotropic cell growth inArabidopsis
Authors: Korolev Andrey V. , Buschmann Henrik , Doonan John H. , Lloyd Clive W.
Published: June 2007

AtMAP70-5 is the most divergent of a recently described multigene family of plant-specific microtubule-associated proteins (MAPs). It is significantly smaller than other members and has several isoform-specific sequence features. To confirm that this protein still functions as a MAP we show that it directly binds microtubules in vitro and decorates microtubules in vivo. When added to tubulin polymerization assays, AtMAP70-5 increases the length distribution profile of microtubules indicating that it stabilizes microtubule dynamics. The overexpressed fusion protein perturbs cell polarity in cell suspensions by inducing extra poles for growth. Similarly, in Arabidopsis plants the overexpression of AtMAP70-5 causes epidermal cells to swell; it also stunts growth and induces right-handed organ twisting. RNAi-mediated downregulation of AtMAP70-5 results in reduced inflorescence stem length and diameter and individual cells are inhibited in their capacity for expansion. These observations suggest that the control over AtMAP70-5 expression levels is important in order to maintain axial polarity and to ensure regular extension of plant organs.
The C-terminus of ephrin-B1 regulates metalloproteinase secretion and invasion of cancer cells
Authors: Tanaka Masamitsu , Sasaki Kazuki , Kamata Reiko , Sakai Ryuichi
Published: June 2007

Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bi-directional signaling via cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, however, the mechanism by which ephrin-B promotes cancer cell invasion is poorly understood. We show that interaction of ephrin-B1 with the Eph receptor B2 (EphB2) significantly enhances processing of the extracellular domain of ephrin-B1, which is regulated by the C-terminus. Matrix metalloproteinase-8 (MMP-8) is the key protease that cleaves ephrin-B1, and the C-terminus of ephrin-B1 regulates activation of the extracellular release of MMP-8 without requirement of de novo protein synthesis. One possible mechanism by which ephrin-B1 regulates the exocytosis of MMP-8 is the activation of Arf1 GTPase, a critical regulator of membrane trafficking. In support of this hypothesis, activation of ephrin-B1 increased GTP-bound Arf1, and the secretion of MMP-8 was reduced by expression of a dominant-negative mutant of Arf1. Expression of ephrin-B1 promoted the invasion of cancer cells in vivo, which required the C-terminus of ephrin-B1. Our results suggest a novel function of the C-terminus of ephrin-B1 in activating MMP-8 secretion, which promotes the invasion of cancer cells.
Climp-63-mediated binding of microtubules to the ER affects the lateral mobility of translocon complexes
Authors: Nikonov Andrei V. , Hauri Hans-Peter , Lauring Brett , Kreibich Gert
Published: June 2007

Microtubules are frequently seen in close proximity to membranes of the endoplasmic reticulum (ER), and the membrane protein CLIMP-63 is thought to mediate specific interaction between these two structures. It was, therefore, of interest to investigate whether these microtubules are in fact responsible for the highly restricted lateral mobility of the translocon complexes in M3/18 cells as described before. As determined by fluorescence recovery after photobleaching, the breakdown of microtubules caused by drug treatment or by overexpression of the microtubule-severing protein spastin, resulted in an increased lateral mobility of the translocons that are assembled into polysomes. Also, the expression of a CLIMP-63 mutant lacking the microtubule-binding domain resulted in a significant increase of the lateral mobility of the translocon complexes. The most striking increase in the diffusion rate of the translocon complexes was observed in M3/18 cells transfected with a siRNA that effectively knocked down the expression of the endogenous CLIMP-63. It appears, therefore, that interaction of microtubules with the ER results in the immobilization of translocon complexes that are part of membrane-bound polysomes, and may play a role in the mechanism that segregates the rough and smooth domains of the ER.
Three-dimensional kinematics of hummingbird flight
Authors: Tobalske Bret W. , Warrick Douglas R. , Clark Christopher J. , Powers Donald R. , Hedrick Tyson L. , Hyder Gabriel A. , Biewener Andrew A.
Published: June 2007

Hummingbirds are specialized for hovering flight, and substantial research has explored this behavior. Forward flight is also important to hummingbirds,but the manner in which they perform forward flight is not well documented. Previous research suggests that hummingbirds increase flight velocity by simultaneously tilting their body angle and stroke-plane angle of the wings,without varying wingbeat frequency and upstroke: downstroke span ratio. We hypothesized that other wing kinematics besides stroke-plane angle would vary in hummingbirds. To test this, we used synchronized high-speed (500 Hz) video cameras and measured the three-dimensional wing and body kinematics of rufous hummingbirds (Selasphorus rufus, 3 g, N=5) as they flew at velocities of 0-12 m s-1 in a wind tunnel. Consistent with earlier research, the angles of the body and the stroke plane changed with velocity,and the effect of velocity on wingbeat frequency was not significant. However,hummingbirds significantly altered other wing kinematics including chord angle, angle of attack, anatomical stroke-plane angle relative to their body,percent of wingbeat in downstroke, wingbeat amplitude, angular velocity of the wing, wingspan at mid-downstroke, and span ratio of the wingtips and wrists. This variation in bird-centered kinematics led to significant effects of flight velocity on the angle of attack of the wing and the area and angles of the global stroke planes during downstroke and upstroke. We provide new evidence that the paths of the wingtips and wrists change gradually but consistently with velocity, as in other bird species that possess pointed wings. Although hummingbirds flex their wings slightly at the wrist during upstroke, their average wingtip-span ratio of 93% revealed that they have kinematically `rigid' wings compared with other avian species.
On planar laser-induced fluorescence with multi-component fuel and tracer design for quantitative determination of fuel concentration in internal combustion engines
Authors: Stevens R E , Ma H , Stone C R , Walmsley H L , Cracknell R
Published: June 2007

This paper first presents an exposition of the theory relevant to quantitative planar laser-induced fluorescence measurements in an engine, at a level commensurate with the expertise of a specialist engineer. It is intended to provide a grounding in the technique, its theoretical basis, and a source of references. Second, this paper presents the design of a multi-component fuel and fuel tracer set that may be used for quantitative planar laser-induced fluoroscence (PLIF) where time and crank-angle resolved knowledge of the vaporization of different fuel fractions is required. Such a fuel is presented and shown to exceed the specifications of accepted single-component fuel tracers. The fuel distillation characteristics, construction, and key features are discussed in the context of the theory.
Synthetic Multifunctional Nanoarchitecture in Lipid Bilayers: Ion Channels, Sensors, and Photosystems
Authors: Bhosale Rajesh , Bhosale Sheshanath , Bollot Guillaume , Gorteau Virginie , Julliard Marc D , Litvinchuk Svetlana , Mareda Jiri , Matile Stefan , Miyatake Tomohiro , Mora Federico , Perez-Velasco Alejandro , Sakai Naomi , Sisson Adam L , Tanaka Hiroyuki , Tran Duy-Hien
Published: June 2007

The creation of functional materials such as ion channels, porous sensors, or smart photosystems depends critically on our ability to assemble sophisticated, error-free and self-repairing nanoarchitecture in a predictable manner. To address these challenging topics, we often used lipid bilayer membranes as compartmentalizing platform and have introduced rigid-rod molecules as privileged scaffolds that bypass all folding problems because they do not fold. This approach provides access to motifs such as rigid-rod barrels, helices, stacks, slides, and wires that can act as smart, stimuli-responsive photosystems, pores, ion channels, hosts, sensors, and catalysts. The selected examples focus on naphthalenediimides (NDIs), a compact, organizable, colorizable, and functionalizable n-semiconductor. This versatile module is used in rigid-rod molecules to mediate transmembrane anion transport by anion–π interactions, as sticky π-clamp within pore sensors to catch otherwise elusive analytes by aromatic electron donor–acceptor interactions, or in blue, transmembrane π-stack architecture to collect and convert photonic energy. These specific examples with multifunctional NDI nanoarchitecture are of help to outline, on the one hand, possibilities to contribute to advanced functional materials such as multianalyte sensors or solar cells and, on the other hand, to keep on wondering about an enormous structural and functional space waiting to be explored.
Formation of Large Molecular Cluster Anions and Elucidation of Their Electronic Structures
Authors: Mitsui Masaaki , Nakajima Atsushi
Published: June 2007

The present account describes our efforts to understand the microscopic aspects of condense phase phenomena, such as ion solvation in molecular liquids and charge carrier localization in molecular solids, by viewing finite-size molecular clusters as their embryonic forms. In this effort, we efficiently prepared supersonically cooled, isolated molecular cluster anions with up to more than 100 constituent molecules and size-selectively investigated their electronic structures using anion photoelectron spectroscopy. Large anionic clusters of two different types of organic molecule; acetonitrile and naphthalene reported as examples of the noteworthy results obtained in our studies. In these two systems, we found that energetically close anionic isomers coexist over a broad range in size, and their contribution in the photoelectron spectra could be separated using anion beam hole-burning technique. A detailed inspection into the electronic states and size-dependent energetics of each isomer has enabled us to establish a link from the large finite cluster to the infinite bulk system.
Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by Use of a Complex between Polysaccharide and Polynucleotide
Authors: Minari Jusaku , Kubo Takanori , Ohba Hideki , Shimada Naohiko , Takeda Yoich , Karinaga Ryouji , Anada Takahisa , Koumoto Kazuya , Kawazu Takeshi , Nagasaki Takeshi , Shinkai Seiji , Sakurai Kazuo
Published: June 2007

Telomerase, which is highly activated in neoplastic cells, can be a target for antisense therapy, and for that purpose, antisense oligonucleotides (AS ODNs) have to be effectively delivered into cellular nucleus where the target telomerase is present. The present work shows a new strategy to deliver AS ODNs to nucleus by use of a novel complex made from a natural polysaccharide schizophyllan (SPG) and AS ODNs. Nuclear transport is strictly regulated by the nuclear pore size and the related proteins. If the molecular weight of SPG is decreased, the SPG/AS ODN complex should be easily transported, although the stability of the complex decreases with a decrease in the molecular weight. We optimized the molecular weight of SPG to be 25 K. Furthermore, we attached importin-β (a nuclear transport protein) to the side chain of SPG by use of a streptavidin–biotin interaction. When this complex was added to Jurkat cells, the telomerase activity was more suppressed than the naked dose, indicating that the importin-β in the complex induced the nuclear transport of the complexed AS ODN and the AS ODN inhibited the telomerase. The present work shows a new methodology for nuclear anti-sense therapy that should be important in future anti-cancer therapies.