bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of functional electrical stimulation on the physiological cost of gait in people with multiple sclerosis
Authors: Paul L , Rafferty D , Young S , Miller L , Mattison P , McFadyen A
Published: June 2008

Objective

Functional electrical stimulation (FES) is used clinically in the management of drop foot in people suffering from neurological conditions. The aim of the study was to investigate the effects of FES, in terms of speed and physiological cost of gait, in people with multiple sclerosis (pwMS).

Methods

Twelve pwMS and 12 healthy matched controls walked at their own preferred walking speed (PWS) for 5 min around a 10 m elliptical course. Subjects with MS completed the protocol with and without using their FES. In addition, control subjects completed the protocol twice more walking at the same PWS of the pwMS to which they were matched.

Results

Wearing FES lead to a significant improvement in walking speed (0.49 ms−1 and 0.43 ms−1 with and without their FES respectively; P < 0.001) and a significant reduction in the physiological cost of gait (0.41 mL min−1 kg−1 m−1 and 0.46 mL min−1 kg−1 m−1 with and without FES respectively; P = 0.017) in pwMS. The speed of walking, oxygen uptake, and physiological cost were significantly different between pwMS and controls both at preferred and matched speeds. Although pwMS exhibit a higher physiological cost of walking, FES offers an orthotic benefit to pwMS and should be considered as a possible treatment option.
Spastic paretic hemifacial contracture in multiple sclerosis: a neglected clinical and EMG entity
Authors: Koutsis G , Kokotis P , Sarrigiannis P , Anagnostouli M , Sfagos C , Karandreas N
Published: June 2008

Background

Spastic paretic hemifacial contracture (SPHC) is an uncommon condition, originally described as a sign of brainstem neoplasia, characterized by sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis. SPHC has only rarely been reported in the context of multiple sclerosis (MS). To further study and assess the frequency of SPHC in patients with MS.

Methods

We screened clinically 500 consecutive patients with MS for the presence of SPHC and further studied electrophysiologically any cases identified.

Results

We identified two patients who developed the condition during the course of an MS relapse. The estimated frequency of the condition was 0.4%. Both patients had relapsing–remitting MS. SPHC was characterized on Electromyography (EMG) by continuous resting activity of irregularly firing motor unit potentials, associated with impaired recruitment of motor units on voluntary contraction. Myokymic discharges were not present. Blink reflex studies were partly consistent with midpontine lesions in the vicinity of the facial nucleus ipsilateral to SPHC. MRI showed lesions in the ipsilateral dorsolateral midpontine tegmentum.

Conclusions

SPHC constitutes a rare but distinct clinical and EMG entity in patients with MS.
Repeated assessment of neuropsychological deficits in multiple sclerosis using the Symbol Digit Modalities Test and the MS Neuropsychological Screening Questionnaire
Authors: Benedict RHB , Duquin JA , Jurgensen S , Rudick RA , Feitcher J , Munschauer FE , Panzara MA , Weinstock-Guttman B
Published: June 2008

Background

Brief cognitive performance tests and self-report measures of neuropsychological symptoms have been proposed for screening purposes in multiple sclerosis (MS) clinics. To better understand the reliability of screening methods, two tests, the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Screening Questionnaire (MSNQ), were administered to 76 patients with MS and 25 healthy controls, matched on demographic characteristics.

Methods

Tests were administered at monthly intervals, over 6 months. In addition, the Beck Depression Inventory Fast Screen for medical patients (BDIFS) was administered to monitor for changes in depression. Our objectives were to determine the reliability of these measures and the relative contribution of cognitive impairment and depression in predicting self-report MSNQ scores.

Results

Results showed that both the SDMT and MSNQ have good to excellent reproducibility over repeated testing. In MS, there are minimal practice effects over successive tests, in the order of 0.2 SD for SDMT and minimal change in the MSNQ. Regression analyses modeled to predict MSNQ based on SDMT and BDIFS showed significant contribution for both, but with the majority of variance being accounted for depression.

Conclusions

We conclude that these brief screening tests provide some independent information about the mental status of patients with MS and are reliable, even when used in monthly, successive examinations.
EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study
Authors: Sundström P , Nyström L , Jidell E , Hallmans G
Published: June 2008

Objectives and methods

The interaction between the two best documented risk factors (human leukocyte antigen [HLA] class II [DRB1*1501 positivity] and Epstein-Barr virus [elevated Epstein-Barr nuclear antigen 1 (EBNA-1) antibody reactivity]) for multiple sclerosis (MS) was studied in a case-control study of biobank samples from 109 MS cases and 212 matched referents.

Results

Multivariate logistic regression analysis showed that both were statistically significant in both sexes. HLA DRB1*1501-positive referents had higher EBNA-1 reactivity than HLA-negative referents. Less EBNA-1 reactivity was required to increase the MS risk in HLA DRB1*1501-positives than in HLA-negatives.

Conclusion

We suggest that HLA DRB1*1501-positive individuals have an increased vulnerability to EBV-induced autoimmunity.
Critical Literacy for school improvement: an action research project
Authors: Cooper Karyn , White Robert E.
Published: June 2008

This article provides an overview of the integrative process of initiating an action research project on literacy for students `at risk' in a Canadian urban elementary school. As the article demonstrates, this requires development of a school-wide framework, which informs the action research project and desired outcomes, and a shared ownership of this vision by school community and staff. Preliminary understandings provide information and considerations that serve to inform discussions about school/curriculum reform and related concerns about Critical Literacy.
Improving schools for social justice in Lebanon
Authors: Bahous Rima , Nabhani Mona
Published: June 2008

In this article, the researchers discuss school improvement for social justice in Beirut, Lebanon. They introduce the Lebanese context: its schooling systems, the revised Lebanese National Curriculum, and the issues under investigation: socioeconomic, political, as well as inclusion/exclusion. The data were collected through semi-structured interviews with school principals, sample teachers, and through group interviews with students of secondary classes from three different schools catering for students of various socioeconomic statuses. The instruments yielded qualitative data that were analyzed to address the research questions. Findings indicate differences among the three schools in elements of social justice and injustice. Data revealed school and teachers' practices causing students loss of self-esteem and lack of social cohesion, diminished access to the curriculum and inadequate preparation for higher education.
Schools for change: a perspective on school improvement in Pakistan
Authors: Riaz Ismat
Published: June 2008

This article focuses on the deeply unsatisfactory state of public and private schooling in a developing country, Pakistan, and the half-hearted measures employed at improving these schools. In the process, the author explores the negative aspects of the ways in which change has been effected in the country's education system and why these reasons have failed to produce the required results. The `change' factor in education has its own dynamics, and these are highlighted in relation to how change can be brought about in Pakistan's failing school system. Solutions need to be system-wide and then painstakingly monitored and allowed to take hold for any viable improvement to take place.
The Difficulty of Making Reparations Affects the Intensity of Collective Guilt
Authors: Schmitt Michael T. , Miller Daniel A. , Branscombe Nyla R. , Brehm Jack W.
Published: June 2008

We examined how the difficulty of making reparations for the harm done to another group affects the intensity of collective guilt. Men were confronted with information documenting male privilege and were told that they would have a chance to help women and reduce patriarchy by collecting signatures on a petition. We manipulated the difficulty of making reparations by asking participants to collect 5, 50, or 100 signatures. As predicted by Brehm's (1999) theory of emotional intensity, collective guilt was a non-monotonic function of the difficulty of making reparations. Men in the moderate difficulty (50 signatures) condition expressed greater collective guilt than participants in the low (5) or high (100) difficulty conditions. Results are discussed in terms of the implications for the theory of emotional intensity, collective guilt, and collective emotions more generally.
Reactions to Outgroup Authorities' Decisions: The Role of Expected Bias, Procedural Fairness and Outcome Favorability
Authors: Ståhl Tomas , Vermunt Riël , Ellemers Naomi
Published: June 2008

It is argued here that expectations of bias (vs. no bias) play a key role in explaining reactions to decisions made by outgroup authorities. Two experiments demonstrate that decision acceptance (Experiment 1) and intentions to protest against an outgroup authority's decisions (Experiment 2) are affected by procedural fairness when the authority has a reputation of being unbiased, but not when the authority's reputation suggests bias. By contrast, some evidence is also found suggesting that reactions to an outgroup authority's decisions are affected by the favorability of the outcome when the authority has a reputation of being biased, but not when the authority has a reputation of being unbiased. Mediation analyses indicate that two different processes account for these effects.
Situational Flexibility of In-Group-Related Attitudes: A Single Category IAT Study of People with Dual National Identity
Authors: Bohner Gerd , Siebler Frank , González Roberto , Haye Andrés , Schmidt Eike A.
Published: June 2008

An experiment was conducted to examine the situational flexibility of in-group-related attitudes at the implicit and explicit level. Seventy-one men and women with dual, Turkish-German, national identities were asked to think about positive aspects of either their German or their Turkish identity. Later, attitudes toward Germans and Turks were assessed using a single category implicit association test (SC-IAT) and self-report scales. Results showed that attitudes toward Turks were generally more positive than attitudes toward Germans, that SC-IAT scores reflecting attitudes toward Turks and Germans were unrelated, and that the identity priming affected men's, but not women's, SC-IAT scores. This finding is discussed in terms of men's greater flexibility in national identification. Explicit attitude measures were largely unaffected by the priming.
The Structure and Management of Conflict: Fighting or Defending the Status Quo
Authors: De Dreu Carsten K. W. , Kluwer Esther S. , Nauta Aukje
Published: June 2008

Although conflict and negotiation studies have examined symmetrical structures in which both parties want change, or asymmetrical structures in which one party wants change and the other to maintain the status quo, no research provided a direct comparison of both structures. Two experiments were conducted to fill this void. Results show that in asymmetrical structures challengers engage in more problem solving and more contending, have less of a loss frame and perceive less control than defendants, and are perceived be less successful. In symmetrical structures, behavior and attitudes of parties are more alike and there is more reciprocation of problem solving and yielding. Furthermore, findings reveal that challengers see their defendant as less friendly and more dominant than defendants see their challengers. Finally, no evidence was obtained that social value orientation moderates these effects. Implications for conflict theory and research, and for third party interventions in symmetrical versus asymmetrical conflicts, are discussed.
Leader—Follower Effects in Resource Dilemmas: The Roles of Leadership Selection and Social Responsibility
Authors: De Cremer David , van Dijk Eric
Published: June 2008

Previous research on the allocation of scarce resources shows that when people are assigned labels of leader or follower in their group, leaders allocate more of the scarce resources to themselves than followers do. In three laboratory studies, we examine the idea that how people are selected for the leader role (i.e. election or appointment) determines whether leaders take more or equal shares (relative to followers) from a common resource. In a first experiment, we show that participants were more accepting of norm violating behavior by an appointed versus elected leader. In a second experiment, we show that when participants were assigned to a leader or follower role, allocations of appointed leaders differed significantly from those of elected leaders and followers, whereas there was no difference between the two latter conditions. Moreover, elected leaders were shown to feel more social responsibility than both appointed leaders and followers. In a final experiment, we show that when participants were primed with the concept of social responsibility (relative to a neutral condition) no difference in allocations between appointed and elected leaders emerged.
`How Many of Us Are There?': Group Size Uncertainty and Social Value Orientations in Common Resource Dilemmas
Authors: de Kwaadsteniet Erik W. , van Dijk Eric , Wit Arjaan , De Cremer David
Published: June 2008

In two studies, we investigate the effects of group size (un)certainty and social value orientations in common resource dilemmas. By focusing on this largely unexplored type of environmental uncertainty, we show that, in contrast to the often replicated finding that resource size uncertainty leads to over-harvesting in common resource dilemmas, group size uncertainty is not necessarily detrimental to the collective interest. Furthermore, we argue and show that whereas under group size certainty people base their individual harvests on the equal division rule, under group size uncertainty they base their harvests on their own social value orientations: whereas under group size certainty both proselfs and pro-socials harvest about an equal share of the common resource, under uncertainty prosocials show self-restraint in order to further their group's outcomes.
Attribution and Categorization Effects in the Representation of Gender Stereotypes
Authors: Krueger Joachim I. , Hall Julie H. , Villano Paola , Jones Meredith C.
Published: June 2008

Social stereotypes involve judgments of how typical certain personality traits are of a group. According to the attribution hypothesis, judgments of trait typicality depend on the perceived prevalence of the trait in the target group. According to the categorization hypothesis, such judgments depend on the degree to which a trait is thought to be more or less prevalent in the target group than in a relevant comparison group. A study conducted with women and men as target groups showed that the attribution hypothesis fit the data best when typicality ratings were made in an absolute format. When, however, typicality ratings were made in a comparative format (how typical is the trait of women as compared with men?), both hypotheses received support. Analytical derivation, supported by empirical evidence, showed an inverse relationship between the size of perceived group differences and their weight given in stereotyping. Implications for stereotype measurement and the rationality of social perception are discussed.
Curricular transposition in citizenship education
Authors: McCowan Tristan
Published: June 2008

The considerable debate in recent years on the aims of citizenship education has not been accompanied by an equally substantial discussion on the educational processes involved.This article puts forward a theoretical framework, referred to as `curricular transposition', for understanding the complex task of realizing normative ideals of citizenship through education. The framework highlights four stages in the educational process: the ideals and aspirations underlying an initiative; the curricular programme designed to achieve them; the programme's implementation in practice; and its effects on students. The `leaps' between these stages — involving movement between ends and means and between ideal and real — are highly problematic.These ideas are explored in the context of an empirical case: the `Voter of the Future' programme in Brazil. Disjunctures are observed at the different stages — in particular, a lack of `harmony' between ends and means, and a lack of teacher ownership of the initiative in the process of implementation — leading to divergence between the initial aims and actual effects. Finally, broader implications of the curricular transposition framework for citizenship education are drawn out.
Education for sustainable human development: Towards a definition
Authors: Landorf Hilary , Doscher Stephanie , Rocco Tonette
Published: June 2008

Three years into the Decade of Education for Sustainable Development, there has been considerable discussion regarding education for sustainable development (ESD) at a policy level, yet very few countries and communities have moved to integrate ESD into their educational curriculum. In this article we argue that the conceptualization and implementation of ESD can be advanced by grounding it in the human capability approach.We define education for sustainable human development as educational practice that results in the enhancement of human well-being, conceived in terms of the expansion of individuals' agency, capabilities and participation in democratic dialogue, both for now and for future generations.We conclude that incorporating Amartya Sen's human capability approach as the basis of ESD will provide the clarity of direction and purpose needed for the transformation of curriculum, pedagogy and assessment.
Star-Spangled Ghibli: Star Voices in the American Versions of Hayao Miyazaki's Films
Authors: Denison Rayna
Published: June 2008

This article offers an examination of the use of American stars in re-voicing a set of Japanese animated texts. The author argues that a new industrial, contextual and textual understanding of stardom is required to penetrate the dense network of meanings attached to star voices in animation. Furthermore, she utilizes a mixed textual and contextual approach to several of Studio Ghibli's American DVD releases to consider the markets for and meanings of anime in America. In so doing this article represents an intervention into a range of academic debates around the nature of contemporary stardom and the significance of anime in America.
Nervous Light Planes
Authors: Gfader Verina
Published: June 2008

Electronic streams appear to be most illuminating when they fail or break down. At these moments, they make apparent our desire of wanting to keep continuity, to experience things uninterruptedly. In the contemporary artistic environment marked by electronic pulses and lightscapes, the flickering screen, with its conflicting modes of engagement, provides the thinking of a limit and erasure. Philippe Parreno's analogue line animation What Do You Believe, Your Eyes or My Words? Speaking Drawing: . . . (2007) inhabits such a corruptive site of `no single continuing line' where the various time structures inherent to the work resist to create unity, both in terms of the work's spatiality and its relation to our sense of time. In Semiconductor's digital piece Inaudible Cities: Part One (2002) the flickering strips the image of the failed electronic stream, its supposedly essential element. The animated cityscape presents us with yet another kind of electronic light movement co-dependent on the sonic pressures of an electrical storm. What is expressed is the process of image-forming itself, the image's potential for self-variation which is linked to imagination and Brian Massumi's `vagueness of the virtual'. Referring to notions such as Gilles Deleuze's `point flicker' or Massumi's `imaginative and non-systemic', the article addresses the sensation of flickering as an experience of spacing and rupturing inherent to animation. Not only does this sensation propose animation as an often paradoxical work, but, proposing a particular site its image can occupy, it allows us to think of the animated image as an erasure itself, with its potential of becoming art.
Hallucinatory Vision and the Blurring of the Subject in Jeremy Blake's `Time-Based Paintings'
Authors: Hertz Betti-Sue
Published: June 2008

From the turn of the 21st century until his death in 200 Jeremy Blake worked at the convergence of animation, digital technology and painting, synthesizing them through the use of cinematic strategies. This article discusses the debt Blake's early abstract works owe to the experimental animated films of the Visual Music artists and American post-war Color Field painters. During this period, Blake applied his exceptional facility with emerging animation software to sequential figure/ground abstractions based on literary narrative structures. Subsequently, Blake shifted from `time-based painting' to richly textured non-narrative biographical sketches created in collaboration with maverick protagonists in contemporary popular music. The visuality of Blake's hallucinatory moving images intensified emotionally as new digital software became available. The deep hybridity of his visual compositions, transmitted through constant fades and overlays of photo-based images and abstracted color patches, doodles and animation characters, create a richly textured bridge between subjective consciousness and the world of appearances.
Clifford Geertz and the Strong Program: The Human Sciences and Cultural Sociology
Authors: Alexander Jeffrey C.
Published: June 2008

In his massively influential work, Clifford Geertz crystallized core methodological and theoretical elements of a strong program in cultural sociology, a program that argues for a meaning-centered social science. If meaning is to be so central, then the theoretical tools that the humanities have developed to investigate art and language must become central to the human sciences more generally. The `thick descriptions' Geertz proposes for social science are powerful reconstructions of the empirical, not simply detailed observations. Likewise, the local knowledge Geertz valorized is inevitably rooted in more encompassing, global meaning-structures, even while every global theme becomes not enriched but different as it emerges locally. Interests can never be objective, and extra-individual structures are both cultural and social at the same time.Yet, while structures are central, they take form only through contingent process, and intertwining them is what Geertz's turn to performance was about.
Making Friends with Jarvis Cocker: Music Culture in the Context of Web 2.0
Authors: Beer David
Published: June 2008

The movement toward what has been described as Web 2.0 has brought with it some significant transformations in the practices, organization and relations of music culture. The user-generated and web-top applications of Web 2.0 are already popular and widely used, the social networking site MySpace already having more than 130 million members worldwide. By focusing specifically upon the presence of the popular music performer Jarvis Cocker across various Web 2.0 applications, this article seeks to open up a series of questions and create opportunities for research into what is happening in contemporary music culture. This exploratory article lays out an agenda for research into music culture and Web 2.0 that is not only concerned with the implications of Web 2.0 for music, but which also attempts to understand the part played by music in making the connections that form the collaborative and participatory cultures of Web 2.0 and the flickering friendships of social networking sites.
Nathalie Heinich's Sociology of Art — and Sociology from Art
Authors: Danko Dagmar
Published: June 2008

The French sociologist Nathalie Heinich has carried out innovative sociological analyses of the field of art since the 1980s. While she is a major figure in French sociology, most of her books are as yet not translated into English.The article seeks to communicate the main contours of Heinich's ideas to an Anglophone audience, by outlining the nature of her most important works concerned with modern and contemporary art, particularly concentrating on her most recent publications. Heinich's advocacy of a descriptive, interpretative sociology of art — as opposed to a `critical' sociology in the manner of Bourdieu — is depicted and considered. The article also traces out her growing orientation towards the development of a`sociology of values'.
Two opposite signaling outputs are driven by the KIR2DL1 receptor in human CD4+ T cells
Authors: Fourmentraux-Neves Emmanuelle , Jalil Abdelali , Da Rocha Sylvie , Pichon Christophe , Chouaib Salem , Bismuth Georges , Caignard Anne
Published: June 2008

Inhibitory killer Ig–like receptors (KIR), expressed by human natural killer cells and effector memory CD8+ T-cell subsets, bind HLA-C molecules and suppress cell activation through recruitment of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). To further analyze the still largely unclear role of inhibitory KIR receptors on CD4+ T cells, KIR2DL1 transfectants were obtained from a CD4+ T-cell line and primary cells. Transfection of CD4+ T cells with KIR2DL1 dramatically increased the T-cell receptor (TCR)–induced production of interleukin-2 independently of ligand binding but inhibited TCR-induced activation after ligation. KIR-mediated costimulation of TCR activation involves intact KIR2DL1-ITIM phosphorylation, SHP-2 recruitment, and PKC-θ phosphorylation. Synapses leading to activation were characterized by an increase in the recruitment of p-Tyr, SHP-2, and p-PKC-θ, but not of SHP-1. Interaction of KIR2DL1 with its ligand led to a strong synaptic accumulation of KIR2DL1 and the recruitment of SHP-1/2, inhibiting TCR-induced interleukin-2 production. KIR2DL1 may induce 2 opposite signaling outputs in CD4+ T cells, depending on whether the KIR receptor is bound to its ligand. These data highlight unexpected aspects of the regulation of T cells by KIR2DL1 receptors, the therapeutic manipulation of which is currently being evaluated.
TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice
Authors: Zhou Yun , Du Wei , Koretsky Tara , Bagby Grover C. , Pang Qishen
Published: June 2008

Nucleophosmin (NPM) is frequently overexpressed in leukemias and other tumors. NPM has been reported to suppress oncogene-induced senescence and apoptosis and may represent a therapeutic target for cancer. We fused a NPM-derived peptide to the HIV-TAT (TAT-NPMΔC) and found that the fusion peptide inhibited proliferation and induced apoptotic death of primary fibroblasts and preleukemic stem cells. TAT-NPMΔC down-regulated several NF-κB–controlled survival and inflammatory proteins and suppressed NF-κB–driven reporter gene activities. Using an inflammation-associated leukemia model, we demonstrate that TAT-NPMΔC induced proliferative suppression and apoptosis of preleukemic stem cells and significantly delayed leukemic development in mice. Mechanistically, TAT-NPMΔC associated with wild-type NPM proteins and formed complexes with endogenous NPM and p65 at promoters of several antiapoptotic and inflammatory genes and abrogated their transactivation by NF-κB in leu-kemic cells. Thus, TAT-delivered NPM peptide may provide a novel therapy for inflammation-associated tumors that require NF-κB signaling for survival.
The largest prospective warfarin-treated cohort supports genetic forecasting
Authors: Wadelius Mia , Chen Leslie Y. , Lindh Jonatan D. , Eriksson Niclas , Ghori Mohammed J. R. , Bumpstead Suzannah , Holm Lennart , McGinnis Ralph , Rane Anders , Deloukas Panos
Published: June 2008

Genetic variants of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) are known to influence warfarin dose, but the effect of other genes has not been fully elucidated. We genotyped 183 polymorphisms in 29 candidate genes in 1496 Swedish patients starting warfarin treatment, and tested for association with response. CYP2C9*2 and *3 explained 12% (P = 6.63 × 10−34) of the variation in warfarin dose, while a single VKORC1 SNP explained 30% (P = 9.82 × 10−100). No SNP outside the CYP2C gene cluster and VKORC1 regions was significantly associated with dose after correction for multiple testing. During initiation of therapy, homozygosity for CYP2C9 and VKORC1 variant alleles increased the risk of over-anticoagulation, hazard ratios 21.84 (95% CI 9.46; 50.42) and 4.56 (95% CI 2.85; 7.30), respectively. One of 8 patients with CYP2C9*3/*3 (12.5%) experienced severe bleeding during the first month compared with 0.27% of other patients (P = .066). A multiple regression model using the predictors CYP2C9, VKORC1, age, sex, and druginteractions explained 59% of the variance in warfarin dose, and 53% in an independent sample of 181 Swedish individuals. In conclusion, CYP2C9 and VKORC1 significantly influenced warfarin dose and predicted individuals predisposed to unstable anticoagulation. Our results strongly support that initiation of warfarin guided by pharmacogenetics would improve clinical outcome.
SNPAnalyzer 2.0: A web-based integrated workbench for linkage disequilibrium analysis and association analysis
Authors: Yoo Jinho , Lee Youngbok , Kim Yujung , Rha Sun Young , Kim Yangseok
Published: June 2008

Background

Since the completion of the HapMap project, huge numbers of individual genotypes have been generated from many kinds of laboratories. The efforts of finding or interpreting genetic association between disease and SNPs/haplotypes have been on-going widely. So, the necessity of the capability to analyze huge data and diverse interpretation of the results are growing rapidly.

Results

We have developed an advanced tool to perform linkage disequilibrium analysis, and genetic association analysis between disease and SNPs/haplotypes in an integrated web interface. It comprises of four main analysis modules: (i) data import and preprocessing, (ii) haplotype estimation, (iii) LD blocking and (iv) association analysis. Hardy-Weinberg Equilibrium test is implemented for each SNPs in the data preprocessing. Haplotypes are reconstructed from unphased diploid genotype data, and linkage disequilibrium between pairwise SNPs is computed and represented by D', r2 and LOD score. Tagging SNPs are determined by using the square of Pearson's correlation coefficient (r2). If genotypes from two different sample groups are available, diverse genetic association analyses are implemented using additive, codominant, dominant and recessive models. Multiple verified algorithms and statistics are implemented in parallel for the reliability of the analysis.

Conclusion

SNPAnalyzer 2.0 performs linkage disequilibrium analysis and genetic association analysis in an integrated web interface using multiple verified algorithms and statistics. Diverse analysis methods, capability of handling huge data and visual comparison of analysis results are very comprehensive and easy-to-use.
Proteomic analysis of lamellar bodies isolated from rat lungs
Authors: Wang Pengcheng , Chintagari Narendranath Reddy , Narayanaperumal Jeyaparthasarathy , Ayalew Sahlu , Hartson Steven , Liu Lin
Published: June 2008

Background

Lamellar bodies are lysosome-related secretory granules and store lung surfactant in alveolar type II cells. To better understand the mechanisms of surfactant secretion, we carried out proteomic analyses of lamellar bodies isolated from rat lungs.

Results

With peptide mass fingerprinting by Matrix Assisted Laser Desorption/Ionization – Time of Flight mass spectrometry, 44 proteins were identified with high confidence. These proteins fell into diverse functional categories: surfactant-related, membrane trafficking, calcium binding, signal transduction, cell structure, ion channels, protein processing and miscellaneous. Selected proteins were verified by Western blot and immunohistochemistry.

Conclusion

This proteomic profiling of lamellar bodies provides a basis for further investigations of functional roles of the identified proteins in lamellar body biogenesis and surfactant secretion.
Functional characterization of endogenous siRNA target genes in Caenorhabditis elegans
Authors: Asikainen Suvi , Heikkinen Liisa , Wong Garry , Storvik Markus
Published: June 2008

Background

Small interfering RNA (siRNA) molecules mediate sequence specific silencing in RNA interference (RNAi), a gene regulatory phenomenon observed in almost all organisms. Large scale sequencing of small RNA libraries obtained from C. elegans has revealed that a broad spectrum of siRNAs is endogenously transcribed from genomic sequences. The biological role and molecular diversity of C. elegans endogenous siRNA (endo-siRNA) molecules, nonetheless, remain poorly understood. In order to gain insight into their biological function, we annotated two large libraries of endo-siRNA sequences, identified their cognate targets, and performed gene ontology analysis to identify enriched functional categories.

Results

Systematic trends in categorization of target genes according to the specific length of siRNA sequences were observed: 18- to 22-mer siRNAs were associated with genes required for embryonic development; 23-mers were associated uniquely with post-embryonic development; 24–26-mers were associated with phosphorus metabolism or protein modification. Moreover, we observe that some argonaute related genes associate with siRNAs with multiple reads. Sequence frequency graphs suggest that different lengths of siRNAs share similarities in overall sequence structure: the 5' end begins with G, while the body predominates with U and C.

Conclusion

These results suggest that the lengths of endogenous siRNA molecules are consequential to their biological functions since the gene ontology categories for their cognate mRNA targets vary depending upon their lengths.
The trypanosome transcriptome is remodelled during differentiation but displays limited responsiveness within life stages
Authors: Koumandou V Lila , Natesan Senthil Kumar A , Sergeenko Tatiana , Field Mark C
Published: June 2008

Background

Trypanosomatids utilise polycistronic transcription for production of the vast majority of protein-coding mRNAs, which operates in the absence of gene-specific promoters. Resolution of nascent transcripts by polyadenylation and trans-splicing, together with specific rates of mRNA turnover, serve to generate steady state transcript levels that can differ in abundance across several orders of magnitude and can be developmentally regulated. We used a targeted oligonucleotide microarray, representing the strongly developmentally-regulated T. brucei membrane trafficking system and ~10% of the Trypanosoma brucei genome, to investigate both between-stage, or differentiation-dependent, transcriptome changes and within-stage flexibility in response to various challenges.

Results

6% of the gene cohort are developmentally regulated, including several small GTPases, SNAREs, vesicle coat factors and protein kinases both consistent with and extending previous data. Therefore substantial differentiation-dependent remodeling of the trypanosome transcriptome is associated with membrane transport. Both the microarray and qRT-PCR were then used to analyse transcriptome changes resulting from specific gene over-expression, knockdown, altered culture conditions and chemical stress. Firstly, manipulation of Rab5 expression results in co-ordinate changes to clathrin protein expression levels and endocytotic activity, but no detectable changes to steady-state mRNA levels, which indicates that the effect is mediated post-transcriptionally. Secondly, knockdown of clathrin or the variant surface glycoprotein failed to perturb transcription. Thirdly, exposure to dithiothreitol or tunicamycin revealed no evidence for a classical unfolded protein response, mediated in higher eukaryotes by transcriptional changes. Finally, altered serum levels invoked little transcriptome alteration beyond changes to expression of ESAG6/7, the transferrin receptor.

Conclusion

While trypanosomes regulate mRNA abundance to effect the major changes accompanying differentiation, a given differentiated state appears transcriptionally inflexible. The implications of the absence of a transcriptome response in trypanosomes for both virulence and models of life cycle progression are discussed.
Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canisin mice
Authors: Liao Chien-Wei , Fan Chia-Kwung , Kao Ting-Chang , Ji Dar-Der , Su Kua-Eyre , Lin Yun-Ho , Cho Wen-Long
Published: June 2008

Background

Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor β1 (TGF-β1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), β-amyloid precursor proteins (AβPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae ofToxocara caniscan invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT.

Methods

BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250T. canisembryonated eggs was investigated from 3 days (dpi) to 8 weeks post-infection (wpi) by Western blotting and RT-PCR.

Results

Results revealed that at 4 and 8 wpi,T. canislarvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-β1, S100B, NF-L, tTG, AβPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain.

Conclusion

Further studies are needed to determine whether there is an increased risk of CT progression into neurodegenerative disease because neurodegeneration-associated AβPP and phosphorylated tau emerged in the brain.
Human Papillomavirus type distribution in invasive cervical cancer in Uganda
Authors: Odida Michael , de Sanjosé Silvia , Quint Wim , Bosch Xavier F , Klaustermeier Joellen , Weiderpass Elisabete
Published: June 2008

Background

We conducted a study aiming to describe Human Papillomavirus (HPV) type distribution in invasive cervical carcinoma in Uganda.

Methods

191 archival cervical carcinoma samples diagnosed in the Department of Pathology, Makerere University in Kampala between 1968 and 1992 were analysed using a sensitive PCR-Reverse Hybridization Line Probe Assay.

Results

Out of the 186 cases of confirmed invasive cervical cancer in the study paraffin blocks, 114 were positive for HPV DNA. Specific HPV genotypes were identifiable in 109 cases: HPV 16, 18, 31, 35, 39, 44, 45, 51, 52 and 70. These occurred as single infections in 105 cases (96.3%) and as multiple infections in 4 cases (3.7%). HPV 16 or 18 accounted for 80% (84/105) of cases with single infection.

Conclusion

The results of this study confirm the role of HPV 16 and 18 in cervical cancer pathogenesis in the Ugandan population. The results suggest that the currently available HPV vaccines against HPV 16 and 18 could possibly prevent the majority of invasive cervical cancers in Uganda.
Biomechanical comparison of lumbar spine instability between laminectomy and bilateral laminotomy for spinal stenosis syndrome – an experimental study in porcine model
Authors: Tai Ching-Lung , Hsieh Pang-Hsing , Chen Weng-Pin , Chen Lih-Huei , Chen Wen-Jer , Lai Po-Liang
Published: June 2008

Background

The association of lumbar spine instability between laminectomy and laminotomy has been clinically studied, but the correspondingin vitrobiomechanical studies have not been reported. We investigated the hypothesis that the integrity of the posterior complex (spinous process-interspinous ligament-spinous process) plays an important role on the postoperative spinal stability in decompressive surgery.

Methods

Eight porcine lumbar spine specimens were studied. Each specimen was tested intact and after two decompression procedures. All posterior components were preserved in Group A (Intact). In Group B (Bilateral laminotomy), the inferior margin of L4 lamina and superior margin of L5 lamina were removed, but the L4–L5 supraspinous ligament was preserved. Fenestrations were made on both sides. In Group C (Laminectomy) the lamina and spinous processes of lower L4 and upper L5 were removed. Ligamentum flavum and supraspinous ligament of L4–L5 were removed. A hydraulic testing machine was used to generate an increasing moment up to 8400 N-mm in flexion and extension. Intervertebral displacement at decompressive level L4–L5 was measured by extensometer

Results

The results indicated that, under extension motion, intervertebral displacement between the specimen in intact form and at two different decompression levels did not significantly differ (P> 0.05). However, under flexion motion, intervertebral displacement of the laminectomy specimens at decompression level L4–L5 was statistically greater than in intact or bilateral laminotomy specimens (P= 0.0000963 andP= 0.000418, respectively). No difference was found between intact and bilateral laminotomy groups. (P> 0.05).

Conclusion

We concluded that a lumbar spine with posterior complex integrity is less likely to develop segment instability than a lumbar spine with a destroyed anchoring point for supraspinous ligament.
Expression of HIV-1 antigens in plants as potential subunit vaccines
Authors: Meyers Ann , Chakauya Ereck , Shephard Enid , Tanzer Fiona L , Maclean James , Lynch Alisson , Williamson Anna-Lise , Rybicki Edward P
Published: June 2008

Background

Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit inNicotianaspp. using transgenic plants and transient expression viaAgrobacterium tumefaciensand recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice.

Results

Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, theAgrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by agagDNA vaccine, pTHGagC.

Conclusion

Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine.
Hemispheric Lateralization of a Molecular Signal for Pain Modulation in the Amygdala
Authors: Carrasquillo Yarimar , Gereau Robert W
Published: June 2008

The extracellular signal-regulated kinase (ERK) cascade has been shown to be a key modulator of pain processing in the central nucleus of the amygdala (CeA) in mice. ERK is activated in the CeA during persistent inflammatory pain and this activation is both necessary and sufficient to induce peripheral tactile hypersensitivity. Interestingly, biochemical studies show that inflammation-induced ERK activation in the CeA only occurs in the right, but not the left hemisphere. This inflammation-induced ERK activation in the right CeA is independent of the side of peripheral inflammation, suggesting that there is a dominant role of the right hemisphere in the modulation of pain by ERK activation in the CeA. However, the functional significance of this biochemical lateralization has yet to be determined. In the present study, we tested the hypothesis that modulation of pain by ERK signaling in the CeA is functionally lateralized. We acutely blocked ERK activation in the CeA by infusing the MEK inhibitor U0126 into the right or the left hemisphere and then measured the behavioral effects on inflammation-induced mechanical hypersensitivity in mice. Our results show that blockade of ERK activation in the right, but not the left CeA, decreases inflammation-induced peripheral hypersensitivity independent of the side of peripheral injury. These findings demonstrate that modulation of pain by ERK signaling in the CeA is functionally lateralized to the right hemisphere, suggesting a dominant role of the right amygdala in pain processing.