bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexural Tests of Phenol Formaldehyde and Slg Composites: Pilot Study
Authors: Cardona F. , Rogers D. , Gurney R. , Trada M. , Ku H.
Published: October 2008

Phenol formaldehyde was filled with Envirospheres slg to increase the strength of the composite for structural applications by a research center on composites, University of Southern Queensland (USQ). In order to reduce costs, the center wished to fill with as much slg as possible, subject to maintaining sufficient strength of the composites in structural applications. This project varied the wt% of the slg in the composites which were then subjected to flexural tests. The results showed that composite with 25 wt% of the slg produced the highest flexural strength and Young’s modulus combined with a reasonable fluidity for casting; the highest flexural strain was achieved when the slg was 10 wt%.
The Power of Peers: Why Some Students Bully Others to Conform
Authors: Burns Sharyn , Maycock Bruce , Cross Donna , Brown Graham
Published: October 2008

Utilizing an interactionist perspective, two associated sensitizing constructs, and a combination of social psychological theory, this article reports on the influence of the peer group on individual perceptions, and its impact on initiation and persistence of bullying. The specific research question, “How does the need to conform with peers and the peer group influence the initiation and persistence of bullying others?” is investigated. Semistructured, one-on-one interviews with a purposive sample of 51 Grade 7 students (aged 12 years) were conducted during school time to investigate factors that influence students to bully others and what might help them to stop. Emerging from the theme of peer group was the need for belonging and group status, in particular social norms or the need to conform, which was influential when students described why they initiated and persisted with bullying others. The influence of labeling, the group process, and the aspiration to be like others within their group emerged as key constructs. The implications of these data for schools will be described and recommendations made.
Exploring the Temporal Dimension in Cancer Patients' Experiences of Nonbiomedical Therapeutics
Authors: Broom Alex , Tovey Philip
Published: October 2008

To date, research on complementary and alternative medicine (CAM) use by cancer patients has tended to provide a “snapshot” of experience, with little attention given to the evolution of experience over time. Drawing on data from solicited diaries, this article examines individual cancer patients' temporal experiences of CAM. Our findings suggest that experiences of CAM are variable over time and space, and furthermore, that the everyday act of “doing CAM” is considerably more problematic than is often reported in face-to-face interview or survey studies. This is explored in relation to the tension between the perceived need for restrictive self-discipline alongside a sense of the emancipatory potential of CAM; the role of CAM therapists in reconceptualizing disease; and the complex interplay between CAM-derived notions of self-healing and acceptance of individual mortality. We argue that an emphasis on the temporality of cancer patients' CAM engagement is necessary to access a more nuanced understanding of the lived experiences of cancer patients.
Life After Burn Injury: Striving for Regained Freedom
Authors: Moi Asgjerd Litleré , Gjengedal Eva
Published: October 2008

Focusing beyond survival, the priority of modern burn care is optimal quality of life. Our aim with this study, which was informed by phenomenology, was to describe and identify invariant meanings in the experience of life after major burn injury. Fourteen adults having sustained a major burn were interviewed, on average, 14 months postinjury, and asked about their experience of important aspects of life. The accident meant facing an extreme situation that demanded vigilance, appropriate action, and the need for assistance. The aftermath of the burn injury and treatment included having to put significant effort into creating coherence in their disrupted personal life stories. Continuing life meant accepting the unchangeable, including going through recurrent processes of enduring, grief, fatalism, comparisons with others, and new feelings of gratefulness. Furthermore, a continuous struggle to change what was changeable, to achieve personal goals, independence, relationships with others, and a meaningful life, were all efforts to regain freedom, aiming for a life as it was before—and sometimes even better.
Sentinels of Safety: Service Dogs Ensure Safety and Enhance Freedom and Well-Being for Families With Autistic Children
Authors: Burrows Kristen E. , Adams Cindy L. , Spiers Jude
Published: October 2008

Children with autism might display unpredictable and volatile behavior that places them in considerable physical danger and creates stress for the family. Families of autistic children often have limited freedom and experience difficulty with everyday activities. In this qualitative ethology study, we examined the effect of integrating service dogs into ten families with an autistic child. Data included participant observation, video recordings of family—parent—dog interaction, and semistructured interviews with the parents. The themes were (a) the dog as a sentinel of safety, (b) gaining freedom through enhanced safety, facilitating public outings and family activities, and (c) improving social recognition and status, in which the presence of the dog promoted awareness of autism and affected social interaction. The triadic relationship between parent, autistic child, and service dog constantly evolves. This research provides valuable information for parents interested in having a service dog for their autistic child, and has implications for long-term human—animal companionship for children with special needs and their caregivers.
Effectiveness of an Integrated Ward-based Program in Preparing Medical Students to Care for Patients at the End of Life
Authors: Ellman Matthew S. , Rosenbaum Julie R. , Cherlin Emily , Bia Margaret
Published: October 2008

Integrating end-of-life care training into the clinical years of medical school has been promoted to enhance education in this area. To assess the effectiveness of an end-of-life care exercise integrated into clinical clerkships, we compared the level of preparedness in end-of-life care reported by students who did or did not complete the exercise. A greater proportion of students who completed the exercise compared with those who did not felt prepared in end-of-life care [50.7% (39/77) vs 35.6% (64/180); P = .02]. Among 5 domains of skills examined, significant differences were seen in interviewing/communicating (3.7 vs 3.5; P = .05) and management of common symptoms (3.3 vs 3.0; P < .01). We conclude that a ward-based integrated end-of-life care exercise may improve graduating students' self-reported preparedness to care for patients at the end of life.
Changes in Caregiver Strain Over Time in Young Adolescents With ADHD
Authors: Evans Steven W. , Sibley Maggie , Serpell Zewelanji N.
Published: October 2008

Objective: The objectives of this study were to identify the relationships between caregiver strain among parents of young adolescents with ADHD and child characteristics during a 1-year period. Method: Parents of 52 middle-school-aged youth with ADHD participated in this study and completed two evaluations 1 year apart. Results: Ratings of oppositional and delinquent behavior best predicted levels of caregiver strain, and change over time did not significantly add to the equation. Patterns of change in caregiver strain indicated important individual differences. Conclusion: Oppositional, delinquent behavior was the best predictor of caregiver strain and suggests that preventing and treating these child behavior problems should be a high priority when working with young adolescents with ADHD. Given the variability in parent responses to changes in oppositional and delinquent behavior, it may also be important to address personal coping strategies for parents of youth exhibiting high rates of these behaviors. ( J. of Att. Dis. 2009; 12(6) 516-524)
Symmetrical Facing Wrinkling of Composite Sandwich Panels
Authors: Lopatin A.V. , Morozov E.V.
Published: October 2008

The article presents the solution of symmetrical face sheet wrinkling problem for sandwich panel with composite facings and an orthotropic core. The new model is proposed for elastic core that takes into account compressive and shear stiffnesses as well as nonlinear change of transverse displacement over the core thickness at wrinkling. The governing buckling equation is derived using energy method. Analysis of cylindrical face wrinkling is performed for sandwich strips subjected to compressive loads applied to the two opposite simply supported edges. The effects of elastic and geometric parameters on the critical buckling stresses and wrinkling waves' formation are examined.
Quasi-Static and Low-Velocity Impact Response of Fully Backed or Simply Supported Sandwich Beams
Authors: Sadighi M. , Pouriayevali H.
Published: October 2008

The present paper describes analysis of low-velocity transverse impact on sandwich beam, with composite faces from Eglass/epoxy and cores from Polyurethane or PVC. Boundary conditions are fully backed rigid or simply supported. This research is based on a step by step study to generate more reliable impact results. Indentation of laminated beam, indentation of sandwich beams, and three-point loading have been analyzed with existing theories and modeled with the FE code ABAQUS, also their results are compared with experimental results. In quasi-static three-point bending, energy is consumed through three mechanisms: indentation of laminated beam, indentation of sandwich beam, and bending of sandwich beam. Impact on fully backed specimen is modeled in two cases of impactor energies using mass spring model of SDOF (single-degree-of-freedom) and indentation stiffness, lower energy of impactor for elastic indentation of sandwich beams, and higher energy for indentation in plastic area. TDOF (two-degree-of-freedom) with flexural and contact stiffnesses are used for impact on simply supported beams. Impacts are simulated by ABAQUS, as well. Results can describe response of beam and impactor displacements in terms of core and faces thicknesses, core material, and impactor energies for static and impact results. The experimental results are in good agreement with the analytical and FE analyses.
Communication in archaeology
Authors: Harding Anthony
Published: October 2008

Communicating archaeology from one person or group to another is beset with problems. The media, the public and students all have different requirements, while the language in which they are addressed – both the spoken language and the intellectual framework or discourse – can act as a disincentive to understanding. Big changes are in store for archaeologists and for other members of the academic community as electronic publication takes over from traditional methods of dissemination such as the printed book. Archaeologists must be prepared for these changes, and should endeavour to put their findings across in a way that interests and stimulates their audience.
Archaeology journals, academics and Open Access
Authors: Carver Martin
Published: October 2008

Martin Carver connects academic peer review with the new technologies of publishing, particularly ‘Open Access’. He recommends the development of four tiers of output: (1) the popular and commercial magazine printed in hard copy and supported by subscribers; (2) the national Open Access online journal, successor to the local journal and supported by local sponsorship; (3) the international Open Access peer-reviewed online journal, representing an intellectual or geographical research area and supported by subsidies and grants via authors. The European Journal of Archaeology is seen as an example. (4) The fourth tier is represented by a global journal such as Antiquity, serving all countries equally and maintaining its political, academic, and commercial independence through reader subscriptions.
Archaeology, communication, and multiple stakeholders: From the other side of the Big Pond
Authors: Levy Janet E.
Published: October 2008

This article reviews discussions and debates about effective communication within North American archaeology. The development of cultural resource management and the expansion of Native American control over archaeology have both influenced the practice and communication of archaeology. The concept of diverse stakeholders derives from discussions about ethics in archaeology, but is relevant to understanding the complexities of archaeological communication. Rather than focus on criticisms of archaeological communication, various examples of effective communication are provided.
Journalists and archaeologists: Notes on dealing constructively with the mass media
Authors: Scherzler Diane
Published: October 2008

Over the past few decades the mass media have increasingly shaped public awareness. For many people, television, the radio, or the press are the only sources for archaeological topics and it is essential, therefore, to be able to collaborate with the world of journalism. It is not only sensational news stories that have an opportunity of being covered by the media, but also serious issues – provided that they are well told. Communicating scientific results to an audience outside one's own specialist subject is, however, not only a question of good will, but also of skill. This article focuses on how to get the attention of the mass media, how to exert influence on the quality of a newspaper article, radio or film, and how to communicate what is really important. It provides an overview of public and media relations and tries to give some helpful suggestions.
Accessibility: Global Gateway to Health Literacy
Authors: Perlow Ellen
Published: October 2008

Health literacy, cited as essential to achieving Healthy People 2010’s goals to “increase quality and years of healthy life” and to “eliminate health disparities,” is defined by Healthy People as “the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.” Accessibility, by definition, the aforementioned “capacity to obtain,” thus is health literacy’s primary prerequisite. Accessibility’s designation as the global gateway to health literacy is predicated also on life’s realities: global aging and climate change, war and terrorism, and life-extending medical and technological advances. People with diverse access needs are health professionals’ raison d’être . However, accessibility, consummately cross-cultural and universal, is virtually absent as a topic of health promotion and practice research and scholarly discussion of health literacy and equity. A call to action to place accessibility in its rightful premier position on the profession’s agenda is issued.
Additional Exercises Improve Trunk Performance After Stroke: A Pilot Randomized Controlled Trial
Authors: Verheyden Geert , Vereeck Luc , Truijen Steven , Troch Mark , LaFosse Christophe , Saeys Wim , Leenaerts Els , Palinckx An , De Weerdt Willy
Published: October 2008

Background. Sitting balance and the ability to perform selective trunk movements are important predictors of functional outcome after stroke. However, studies evaluating the effect of exercises aimed at improving trunk performance are sparse. Objective. To examine the effect of additional trunk exercises on trunk performance after stroke. Methods. An assessor-blinded randomized controlled trial was carried out at an inpatient stroke rehabilitation center. In total 33 participants were assigned to an experimental group (n = 17) or a control group (n = 16). In addition to conventional therapy, the experimental group received 10 hours of individual and supervised trunk exercises; 30 minutes, 4 times a week, for 5 weeks. Trunk performance was evaluated by the Trunk Impairment Scale (TIS) and its subscales of static and dynamic sitting balance and coordination. A general linear repeated measures model was used to analyze the results of our study. Results. No significant differences were found pretreatment between the 2 groups for the collected demographic variables, stroke-related parameters, clinical measures, number of therapy sessions received, and primary outcome measure used. Posttreatment, a significantly better improvement was noted in the experimental group compared to the control group for the dynamic sitting balance subscale only; measuring selective lateral flexion initiated from the upper and lower part of the trunk, ( P = .002, post hoc power calculation = .90, effect size = 1.16). Conclusions. Our results suggest that, in addition to conventional therapy, trunk exercises aimed at improving sitting balance and selective trunk movements have a beneficial effect on the selective performance of lateral flexion of the trunk after stroke.
The Relationship of Sales and Marketing Expenses to Hotel Performance in the United States
Authors: O'Neill John W. , Hanson Bjorn , Mattila Anna S.
Published: October 2008

While hotel organizations are investing considerable sums of money for marketing at the unit level, research investigating the relative benefits of the different areas where those funds can be invested is lacking. This exploratory study endeavors to fill that void. Since different types of hotels have differing operating characteristics, this study examines marketing expenditures for various hotel tiers, using the Smith Travel Research chain scale categorizations. The study finds that marketing expenditures have differential effects according to the type of hotel and the particular type of marketing expenditure. These analyses explore implications of various types of marketing expenses on both hotel unit revenue and profitability.
Accounting for Human Resource Flexibility
Authors: Tracey J. Bruce
Published: October 2008

The accompanying article argues strongly for the proposition that a hotel's business strategy is related to its human resources policies. However, the conceptual framework in the article does not go into sufficient depth; nor does it seem to reflect existing research on HR system flexibility, that is, the extent to which employees can be directed to address a wide range of business activities.
Using a Modular System Approach to International Franchising
Authors: Miller Brian
Published: October 2008

International expansion faces numerous constraints, notably, those stemming from language and culture. A modular approach to international franchising suggests a mechanism that might have made for a more successful outcome for the Polish operator in the accompanying case. By dividing the elements that constitute a restaurant concept into core items and peripheral items, the modular approach allows for both necessary consistency and necessary alterations. These core and peripheral elements fall into three general categories: operations, branding, and marketing.
Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism
Authors: Lambe Teresa , Simpson Robert J. , Dawson Sara , Bouriez-Jones Tiphaine , Crockford Tanya L. , Lepherd Michelle , Latunde-Dada Gladys O. , Robinson Hannah , Raja Kishor B. , Campagna Dean R. , Villarreal Guadalupe , Ellory J. Clive , Goodnow Christopher C. , Fleming Mark D. , McKie Andrew T. , Cornall Richard J.
Published: October 2008

Hereditary forms of iron-deficiency anemia, including animal models, have taught us much about the normal physiologic control of iron metabolism. However, the discovery of new informative mutants is limited by the natural mutation frequency. To address this limitation, we have developed a screen for heritable abnormalities of red blood cell morphology in mice with single-nucleotide changes induced by the chemical mutagen ethylnitrosourea (ENU). We now describe the first strain, fragile-red, with hypochromic microcytic anemia resulting from a Y228H sub-stitution in the ferrireductase Steap3 (Steap3Y288H). Analysis of the Steap3Y288H mutant identifies a conserved motif required for targeting Steap3 to internal compartments and highlights how phenotypic screens linked to mutagenesis can identify new functional variants in erythropoiesis and ascribe function to previously unidentified motifs.
Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33
Authors: Pecaric-Petkovic Tatjana , Didichenko Svetlana A. , Kaempfer Sacha , Spiegl Nicole , Dahinden Clemens A.
Published: October 2008

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcϵRI-activation, and enhances FcϵRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-κB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.
Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML
Authors: Zeng Zhihong , Xi Shi Yue , Samudio Ismael J. , Wang Rui-Yu , Ling Xiaoyang , Frolova Olga , Levis Mark , Rubin Joshua B. , Negrin Robert R. , Estey Elihu H. , Konoplev Sergej , Andreeff Michael , Konopleva Marina
Published: October 2008

SDF-1α/CXCR4 signaling plays a key role in leukemia/bone marrow microenvironment interactions. We previously reported that bone marrow–derived stromal cells inhibit chemotherapy-induced apoptosis in acute myeloid leukemia (AML). Here we demonstrate that the CXCR4 inhibitor AMD3465 antagonized stromal-derived factor 1α (SDF-1α)–induced and stroma-induced chemotaxis and inhibited SDF-1α–induced activation of prosurvival signaling pathways in leukemic cells. Further, CXCR4 inhibition partially abrogated the protective effects of stromal cells on chemotherapy-induced apoptosis in AML cells. Fetal liver tyrosine kinase-3 (FLT3) gene mutations activate CXCR4 signaling, and coculture with stromal cells significantly diminished antileukemia effects of FLT3 inhibitors in cells with mutated FLT3. Notably, CXCR4 inhibition increased the sensitivity of FLT3-mutated leukemic cells to the apoptogenic effects of the FLT3 inhibitor sorafenib. In vivo studies demonstrated that AMD3465, alone or in combination with granulocyte colony-stimulating factor, induced mobilization of AML cells and progenitor cells into circulation and enhanced antileukemic effects of chemotherapy and sorafenib, resulting in markedly reduced leukemia burden and prolonged survival of the animals. These findings indicate that SDF-1α/CXCR4 interactions contribute to the resistance of leukemic cells to signal transduction inhibitor– and chemotherapy-induced apoptosis in systems mimicking the physiologic microenvironment. Disruption of these interactions with CXCR4 inhibitors represents a novel strategy of sensitizing leukemic cells by targeting their protective bone marrow microenvironment.
Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells
Authors: Tolar Jakub , Ishida-Yamamoto Akemi , Riddle Megan , McElmurry Ron T. , Osborn Mark , Xia Lily , Lund Troy , Slattery Catherine , Uitto Jouni , Christiano Angela M. , Wagner John E. , Blazar Bruce R.
Published: October 2008

The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. We report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders.
Gene expression profiling of peripheral T-cell lymphoma including γδ T-cell lymphoma
Authors: Miyazaki Kana , Yamaguchi Motoko , Imai Hiroshi , Kobayashi Tohru , Tamaru Satoshi , Nishii Kazuhiro , Yuda Masao , Shiku Hiroshi , Katayama Naoyuki
Published: October 2008

The gene expression profile of peripheral γδ T-cell lymphoma (γδTCL) has not been investigated. Using oligonucleotide microarrays, we analyzed total RNA from 7 patients with γδTCL (4 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal) and 27 patients with αβTCL (11 peripheral TCL-unspecified, 15 angioimmunoblastic TCL, and 1 hepatosplenic). Unsupervised microarray analyses classified all hepatosplenic γδTCLs into a single cluster, whereas other γδTCLs were scattered within the αβTCL distribution. We identified a T-cell receptor signature gene set, which accurately classified γδTCL and αβTCL. A classifier based on gene expression under supervised analysis correctly identified γδTCL. One case of hepatosplenic αβTCL was placed in the γδTCL grouping. γδTCL signature genes included genes encoding killer cell immunoglobulin-like receptors and killer cell lectin-like receptors. Our results indicate that hepatosplenic γδTCL is a distinct form of peripheral TCL and suggest that nonhepatosplenic γδTCLs are heterogeneous in gene expression.
Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma
Authors: Ludwig Heinz , Hajek Roman , Tóthová Elena , Drach Johannes , Adam Zdenek , Labar Boris , Egyed Miklós , Spicka Ivan , Gisslinger Heinz , Greil Richard , Kuhn Ingrid , Zojer Niklas , Hinke Axel
Published: October 2008

We compared thalidomide-dexamethasone (TD) with melphalan-prednisolone (MP) in 289 elderly patients with multiple myeloma (MM). Patients received either thalidomide 200 mg plus dexamethasone 40 mg, days 1 to 4 and 15 to 18 on even cycles and days 1 to 4 on odd cycles, during a 28-day cycle or to melphalan 0.25 mg/kg and prednisolone 2 mg/kg orally on days 1 to 4 during a 28- to 42-day cycle. Patients achieving stable disease or better were randomly assigned to maintenance therapy with either thalidomide 100 mg daily and 3 MU interferon α-2b thrice weekly or to 3 MU interferon α-2b thrice weekly only. TD resulted in a higher proportion of complete and very good remissions (26% vs 13%; P = .006) and overall responses (68% vs 50%; P = .002) compared with MP. Time to progression (21.2 vs 29.1 months; P = .2), and progression-free survival was similar (16.7 vs 20.7 months; P = .1), but overall survival was significantly shorter in the TD group (41.5 vs 49.4 months; P = .024). Toxicity was higher with TD, particularly in patients older than 75 years with poor performance status. The study was registered at ClinicalTrials.gov as NCT00205751.
Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency
Authors: Ajzner Éva , Schlammadinger Ágota , Kerényi Adrienne , Bereczky Zsuzsanna , Katona Éva , Haramura Gizella , Boda Zoltán , Muszbek László
Published: October 2008

Acquired factor XIII (FXIII) deficiency due to autoantibody against FXIII is a very rare severe hemorrhagic diathesis. Antibodies directed against the A subunit of FXIII, which interfere with different functions of FXIII, have been described. Here, for the first time, we report an autoantibody against the B subunit of FXIII (FXIII-B) that caused life-threatening bleeding in a patient with systemic lupus erythematosus. FXIII activity, FXIII-A2B2 complex, and individual FXIII subunits were undetectable in the plasma, whereas platelet FXIII activity and antigen were normal. Neither FXIII activation nor its activity was inhibited by the antibody, which bound to structural epitope(s) on both free and complexed FXIII-B. The autoantibody highly accelerated the elimination of FXIII from the circulation. FXIII supplementation combined with immunosuppressive therapy, plasmapheresis, immunoglobulin, and anti-CD20 treatment resulted in the patient's recovery. FXIII levels returned to around 20% at discharge and after gradual increase the levels stabilized above 50%.
HIV-associated lymphomas and gamma-herpesviruses
Authors: Carbone Antonino , Cesarman Ethel , Spina Michele , Gloghini Annunziata , Schulz Thomas F.
Published: October 2008

Among the most common HIV-associated lymphomas are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with immunoblastic-plasmacytoid differentiation (also involving the central nervous system). Lymphomas occurring specifically in HIV-positive patients include primary effusion lymphoma (PEL) and its solid variants, plasmablastic lymphoma of the oral cavity type and large B-cell lymphoma arising in Kaposi sarcoma herpesvirus (KSHV)–associated multicentric Castleman disease. These lymphomas together with BL and DLBCL with immunoblastic-plasmacytoid differentiation frequently carry EBV infection and display a phenotype related to plasma cells. EBV infection occurs at different rates in different lymphoma types, whereas KSHV is specifically associated with PEL, which usually occurs in the setting of profound immunosuppression. The current knowledge about HIV-associated lymphomas can be summarized in the following key points: (1) lymphomas specifically occurring in patients with HIV infection are closely linked to other viral diseases; (2) AIDS lymphomas fall in a spectrum of B-cell differentiation where those associated with EBV or KSHV commonly exhibit plasmablastic differentiation; and (3) prognosis for patients with lymphomas and concomitant HIV infection could be improved using better combined chemotherapy protocols in-corporating anticancer treatments and antiretroviral drugs.
CompMoby: Comparative MobyDick for detection of cis-regulatory motifs
Authors: Chaivorapol Christina , Melton Collin , Wei Grace , Yeh Ru-Fang , Ramalho-Santos Miguel , Blelloch Robert , Li Hao
Published: October 2008

Background

The regulation of gene expression is complex and occurs at many levels, including transcriptional and post-transcriptional, in metazoans. Transcriptional regulation is mainly determined by sequence elements within the promoter regions of genes while sequence elements within the 3' untranslated regions of mRNAs play important roles in post-transcriptional regulation such as mRNA stability and translation efficiency. Identifying cis-regulatory elements, or motifs, in multicellular eukaryotes is more difficult compared to unicellular eukaryotes due to the larger intergenic sequence space and the increased complexity in regulation. Experimental techniques for discovering functional elements are often time consuming and not easily applied on a genome level. Consequently, computational methods are advantageous for genome-wide cis-regulatory motif detection. To decrease the search space in metazoans, many algorithms use cross-species alignment, although studies have demonstrated that a large portion of the binding sites for the same trans-acting factor do not reside in alignable regions. Therefore, a computational algorithm should account for both conserved and nonconserved cis-regulatory elements in metazoans.

Results

We present CompMoby (Comparative MobyDick), software developed to identify cis-regulatory binding sites at both the transcriptional and post-transcriptional levels in metazoans without prior knowledge of the trans-acting factors. The CompMoby algorithm was previously shown to identify cis-regulatory binding sites in upstream regions of genes co-regulated in embryonic stem cells. In this paper, we extend the software to identify putative cis-regulatory motifs in 3' UTR sequences and verify our results using experimentally validated data sets in mouse and human. We also detail the implementation of CompMoby into a user-friendly tool that includes a web interface to a streamlined analysis. Our software allows detection of motifs in the following three categories: one, those that are alignable and conserved; two, those that are conserved but not alignable; three, those that are species specific. One of the output files from CompMoby gives the user the option to decide what category of cis-regulatory element to experimentally pursue based on their biological problem. Using experimentally validated biological datasets, we demonstrate that CompMoby is successful in detecting cis-regulatory target sites of known and novel trans-acting factors at the transcriptional and post-transcriptional levels.

Conclusion

CompMoby is a powerful software tool for systematicde novodiscovery of evolutionarily conserved and nonconserved cis-regulatory sequences involved in transcriptional or post-transcriptional regulation in metazoans. This software is freely available to users athttp://genome.ucsf.edu/compmoby/.
Identification of a small optimal subset of CpG sites as bio-markers from high-throughput DNA methylation profiles
Authors: Meng Hailong , Murrelle Edward L , Li Guoya
Published: October 2008

Background

DNA methylation patterns have been shown to significantly correlate with different tissue types and disease states. High-throughput methylation arrays enable large-scale DNA methylation analysis to identify informative DNA methylation biomarkers. The identification of disease-specific methylation signatures is of fundamental and practical interest for risk assessment, diagnosis, and prognosis of diseases.

Results

Using published high-throughput DNA methylation data, a two-stage feature selection method was developed to select a small optimal subset of DNA methylation features to precisely classify two sample groups. With this approach, a small number of CpG sites were highly sensitive and specific in distinguishing lung cancer tissue samples from normal lung tissue samples.

Conclusion

This study shows that it is feasible to identify DNA methylation biomarkers from high-throughput DNA methylation profiles and that a small number of signature CpG sites can suffice to classify two groups of samples. The computational method we developed in the study is efficient to identify signature CpG sites from disease samples with complex methylation patterns.
Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells
Authors: Kretlow James D , Jin Yu-Qing , Liu Wei , Zhang Wen Jie , Hong Tan-Hui , Zhou Guangdong , Baggett L Scott , Mikos Antonios G , Cao Yilin
Published: October 2008

Background

Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.

Results

Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors.

Conclusion

Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use.
An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10
Authors: Dutton James R , Antonellis Anthony , Carney Thomas J , Rodrigues Frederico SLM , Pavan William J , Ward Andrew , Kelsh Robert N
Published: October 2008

Background

A major challenge lies in understanding the complexities of gene regulation. Mutation of the transcription factor SOX10 is associated with several human diseases. The disease phenotypes reflect the function of SOX10 in diverse tissues including the neural crest, central nervous system and otic vesicle. As expected, the SOX10 expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern.SOX10expression is highly conserved between all vertebrates characterised.

Results

We have combined in vivo testing of DNA fragments in zebrafish and computational comparative genomics to identify the first regulatory regions of the zebrafishsox10gene. Both approaches converged on the 3' end of the conserved 1stintron as being critical for spatial patterning ofsox10in the embryo. Importantly, we have defined a minimal region crucial for this function. We show that this region contains numerous binding sites for transcription factors known to be essential in early neural crest induction, including Tcf/Lef, Sox and FoxD3. We show that the identity and relative position of these binding sites are conserved between zebrafish and mammals. A further region, partially required for oligodendrocyte expression, lies in the 5' region of the same intron and contains a putative CSL binding site, consistent with a role for Notch signalling insox10regulation. Furthermore, we show that β-catenin, Notch signalling and Sox9 can induce ectopicsox10expression in early embryos, consistent with regulatory roles predicted from our transgenic and computational results.

Conclusion

We have thus identified two major sites ofsox10regulation in vertebrates and provided evidence supporting a role for at least three factors in drivingsox10expression in neural crest, otic epithelium and oligodendrocyte domains.
Dual-hemisphere tDCS facilitates greater improvements for healthy subjects' non-dominant hand compared to uni-hemisphere stimulation
Authors: Vines Bradley W , Cerruti Carlo , Schlaug Gottfried
Published: October 2008

Background

Transcranial direct current stimulation (tDCS) is a non-invasive technique that has been found to modulate the excitability of neurons in the brain. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal tDCS increases excitability, whereas cathodal tDCS decreases excitability. Research has shown that applying anodal tDCS to the non-dominant motor cortex can improve motor performance for the non-dominant hand, presumably by means of changes in synaptic plasticity between neurons. Our previous studies also suggest that applying cathodal tDCS over the dominant motor cortex can improve performance for the non-dominant hand; this effect may result from modulating inhibitory projections (interhemispheric inhibition) between the motor cortices of the two hemispheres. We hypothesized that stimultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex would have a greater effect on finger sequence performance for the non-dominant hand, compared to stimulating only the non-dominant motor cortex. Sixteen right-handed participants underwent three stimulation conditions: 1) dual-hemisphere – with anodal tDCS over the non-dominant motor cortex, and cathodal tDCS over the dominant motor cortex, 2) uni-hemisphere – with anodal tDCS over the non-dominant motor cortex, and 3) sham tDCS. Participants performed a finger-sequencing task with the non-dominant hand before and after each stimulation. The dependent variable was the percentage of change in performance, comparing pre- and post-tDCS scores.

Results

A repeated measures ANOVA yielded a significant effect of tDCS condition (F(2,30) = 4.468, p = .037). Post-hoc analyses revealed that dual-hemisphere stimulation improved performance significantly more than both uni-hemisphere (p = .021) and sham stimulation (p = .041).

Conclusion

We propose that simultaneously applying cathodal tDCS over the dominant motor cortex and anodal tDCS over the non-dominant motor cortex produced an additive effect, which facilitated motor performance in the non-dominant hand. These findings are relevant to motor skill learning and to research studies of motor recovery after stroke.
TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy
Authors: Turner Bradley J , Bäumer Dirk , Parkinson Nicholas J , Scaber Jakub , Ansorge Olaf , Talbot Kevin
Published: October 2008

Background

Redistribution of nuclear TAR DNA binding protein 43 (TDP-43) to the cytoplasm and ubiquitinated inclusions of spinal motor neurons and glial cells is characteristic of amyotrophic lateral sclerosis (ALS) pathology. Recent evidence suggests that TDP-43 pathology is common to sporadic ALS and familial ALS without SOD1 mutation, but not SOD1-related fALS cases. Furthermore, it remains unclear whether TDP-43 abnormalities occur in non-ALS forms of motor neuron disease. Here, we characterise TDP-43 localisation, expression levels and post-translational modifications in mouse models of ALS and spinal muscular atrophy (SMA).

Results

TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1G93A mice. In addition, abnormally phosphorylated or truncated TDP-43 species were not detected in fractionated ALS mouse spinal cord or brain. Despite partial colocalisation of TDP-43 with SMN, depletion of SMN- and coilin-positive Cajal bodies in motor neurons of affected SMA mice did not alter nuclear TDP-43 distribution, expression or biochemistry in spinal cords.

Conclusion

These results emphasise that TDP-43 pathology characteristic of human sporadic ALS is not a core component of the neurodegenerative mechanisms caused by SOD1 mutation or SMN deficiency in mouse models of ALS and SMA, respectively.
Isolation and characterization of a T7-like lytic phage for Pseudomonas fluorescens
Authors: Sillankorva Sanna , Neubauer Peter , Azeredo Joana
Published: October 2008

Background

Despite the proven relevance ofPseudomonas fluorescensas a spoilage microorganism in milk, fresh meats and refrigerated food products and the recognized potential of bacteriophages as sanitation agents, so far no phages specific forP. fluorescensisolates from dairy industry have been closely characterized in view of their lytic efficiency. Here we describe the isolation and characterization of a lytic phage capable to infect a variety ofP. fluorescensstrains isolated from Portuguese and United States dairy industries.

Results

Several phages were isolated which showed a different host spectrum and efficiency of lysis. One of the phages, phage ϕIBB-PF7A, was studied in detail due to its efficient lysis of a wide spectrum ofP. fluorescensstrains and ribotypes. Phage ϕIBB-PF7A with a head diameter of about 63 nm and a tail size of about 13 × 8 nm belongs morphologically to thePodoviridaefamily and resembles a typical T7-like phage, as analyzed by transmission electron microscopy (TEM). The phage growth cycle with a detected latent period of 15 min, an eclipse period of 10 min, a burst size of 153 plaque forming units per infected cell, its genome size of approximately 42 kbp, and the size and N-terminal sequence of one of the protein bands, which gave similarity to the major capsid protein 10A, are consistent with this classification.

Conclusion

The isolated T7-like phage, phage ϕIBB-PF7A, is fast and efficient in lysing differentP. fluorescensstrains and may be a good candidate to be used as a sanitation agent to control the prevalence of spoilage causingP. fluorescensstrains in dairy and food related environments.
Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos
Authors: Alcaraz-Pérez Francisca , Mulero Victoriano , Cayuela María L
Published: October 2008

Background

The dual-luciferase assay has been widely used in cell lines to determine rapidly but accurately the activity of a given promoter. Although this strategy has proved very useful, it does not allow the promoter and gene function to be analyzed in the context of the whole organism.

Results

Here, we present a rapid and sensitive assay based on the classical dual-luciferase reporter technique which can be used as a new tool to characterize the minimum promoter region of a gene as well as the in vivo response of inducible promoters to different stimuli. We illustrate the usefulness of this system for studying both constitutive (telomerase) and inducible (NF-κB-dependent) promoters. The flexibility of this assay is demonstrated by induction of the NF-κB-dependent promoters using simultaneous microinjection of different pathogen-associated molecular patterns as well as with the use of morpholino-gene mediated knockdown.

Conclusion

This assay has several advantages compared with the classical in vitro (cell lines) and in vivo (transgenic mice) approaches. Among others, the assay allows a rapid and quantitative measurement of the effects of particular genes or drugs in a given promoter in the context of a whole organism and it can also be used in high throughput screening experiments.