bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiencing Sociology
Authors: Fraser Mariam
Published: February 2009

Using C. Wright Mills' book The Sociological Imagination as a touchstone for its discussion, this article addresses the relations between the sociological problem, relevance and experience as they are and could potentially be understood within sociology. Beginning with the historical relation between sociology, science and literature — a relation which has been productively but differently complicated by poststructuralist and postconstructivist theories — this article asks: to what extent does the empirical offer a referent for the sociological problem? To what is sociology obliged to be relevant? Arguing for the continued relevance of relevance, particularly in the light of recent reforms in higher education in the UK and the USA, the article explores how the sociological problem might be transformed — and perhaps, more importantly, might be transformative — if the basic commitments of a research project were not to historical social structures but to virtual structures.
Testing Powers of Engagement
Authors: Marres Noortje
Published: February 2009

This article explores the role of sustainable living experiments as devices of public engagement. It engages with object-centred perspectives in the sociology of science and technology, which have characterized public experiments as sites for the domestication of technology, and as effective instruments of public involvement, because, in part, of the seductive force of their use of empirical forms of display. Green living experiments, which are conducted in the intimate setting of the home and reported on blogs, complicate this understanding, insofar as they seek to format socio-material practices as sites of involvement. This has implications for how we conceive of the relations between public involvement and everyday material practices. While the latter are often located outside the public sphere, green living experiments extend the publicity genre of `being intimate in public' to things. It also follows that green living experiments do not so much solve but rather articulate problems of public involvement.
Social Science as Reading and Performance
Authors: Reed Isaac , Alexander Jeffrey
Published: February 2009

In the age of the `return to the empirical' in which the theoretical disputes of an earlier era seem to have fallen silent, we seek to excavate the intellectual conditions for reviving theoretical debate, for it is upon this recovery that deeper understanding of the nature and purpose of empirical social science depends. We argue against the all too frequent turn to ontology, whereby critical realists have sought an epistemological guarantor of sociological validity. We seek, to the contrary, to crystallize a culturally-based, hermeneutic account of a rational social science. Derived from disputes within the sociology of culture, on the one hand, and the long-standing concerns of interpretive philosophy, on the other, we offer a cultural-sociological approach to epistemology. We view the production of truth in social science as a reading of a meaningful social world, and as a performance of truth-claims that is constrained by evidence, but whose success depends on other contextual factors. We conclude that the rationality of social science can be achieved only by forgoing ontology. Theories are abstractions of investigators' meanings that allow the interpretation of social meanings in turn, whether those are actions, relations, or structures. Successful explanations are those that intertwine these meaning structures of investigators and actors in an effective way.
Do surgical patients differ in the way they prioritise aspects of hospital care?
Authors: Iversen Maria G. , Hansen Karen S. , Freil Morten , Kreiner Svend
Published: February 2009

Main objective: To investigate whether surgical patients have the same or different priorities within hospital care by examining whether the importance patients ascribe to different aspects of hospital care can be explained by how important they find aspects of hospitalization in general. Background: Few studies have investigated patient priorities within hospital care. Knowledge of patient priorities is important for the purpose of making quality improvements in hospital care. In relation to this, it is important to know whether different groups of patients have qualitative different priorities. Design and subjects: A postal questionnaire was mailed to 3676 surgical patients after discharge from five Danish hospitals. Out of this figure, 2380 participated in the survey and 1597 were qualified for inclusion in the analyses. Analyses: Data was analysed by graphical loglinear Rasch models. Thirty-six hospital care aspects were included in the final model. Main results and conclusions: To a great extent, patients agreed on the prioritised order of the hospital care aspects investigated. Avoidance of errors and professional health care skills had highest priority. Qualitative differences in priorities were mainly found among different age groups; the younger patients found that information was more important than the older patients, who on the other hand found continuity of care to be more important. Quantitative differences were observed, with patients harbouring different views on of the importance of hospital care in general; on average, women rated this slightly more important than men.
Growing Customers
Authors: Tyler Melissa
Published: February 2009

This article seeks to draw together insights from the sociologies of childhood and consumer culture as well as recent research on sales-service work to argue the case for a `paediocular' approach to the study of consumer culture and service work. Such an approach, it is argued here, would draw attention to the ways in which both the presence of children as consumers and dominant social constructions of childhood shape the configuration, management and experience of sales-service work. With reference to the findings of a series of interviews conducted with people in a range of sales-service environments, the analysis presented explores some of the ways in which sales-service providers working on the front line of the children's culture industries are required to socialize customers through the performance of aspirational and proprietary forms of aesthetic and emotional labour. The article also highlights some of the ways in which children's consumer culture involves the landscaping of sales-service environments and worker's bodies, as well as forms of interaction such as sales-service encounters, according to an aspirational and proprietary aesthetic that is designed to be simultaneously enchanting and instrumental.
Between Incas and Indians
Authors: Alcalde M. Cristina
Published: February 2009

Inca Kola is the only national cola to outsell Coca-Cola in its own territory. This article situates the marketing and success of Inca Kola within broader theoretical debates on the relationship between the local and the global and underscores the usefulness of more nuanced understandings of the local by bringing to the forefront internal heterogeneity and local hegemonic discourses. I suggest that Inca Kola is successful in large part because it bridges the gap between the local and the global and the traditional and the modern by presenting an alternative to Coca-Cola's American-global modernity through the construction of a Peruvian-global modernity. I then complicate notions of the local by analyzing how the Peruvian-global modernity represented in Inca Kola's ads is internally hegemonic and suggest that Inca Kola's marketing is better understood in terms of its embeddedness in urban white-mestizo racial hierarchies.
Developing Consumer Subjectivity in Ireland: 1900—80
Authors: Dolan Paddy
Published: February 2009

The development of consumer subjectivity cannot be solely understood in terms of the intentions, strategies and discursive practices emanating from diverse power centres. Following Elias, and using Ireland as an empirical case, the consumer is presented as undergoing a shift along a continuum of We—I balances towards the latter pole. This occurs within the context of increasing social interdependencies, functional specialization and social integration. Through complex, unplanned social processes over time, the consumer is seen more individualistically. I conclude by suggesting that there are opportunities to synthesize figurational and Foucauldian approaches to consumer subjectivity once long-term social change is prioritized.
Theory in action research
Authors: Dick Bob , Stringer Ernie , Huxham Chris
Published: February 2009

In this prologue to the special issue on theory in action research we provide a context and an introduction for the articles that follow. We begin by sketching in some of our shared ideas on theory in action research and some of the differences between our own approaches. Then, after briefly describing the process of preparing this issue, we provide a succinct pointer to each article in the issue.
The `f' word has everything to do with it
Authors: Frisby Wendy , Maguire Patricia , Reid Colleen
Published: February 2009

This article considers how feminist theories have and can contribute to action research, while acknowledging some of the tensions that arise when applying and building feminist theories. While feminist theorizing undoubtedly occurs in some action research, whether it is named or not, the gap appears to be in linking local knowledge to existing theoretical frameworks. Feminist theories, even though they are always partial and contested, have acted as an intentional counter to dominant theories about human experiences and strategies for change. They prompt people to ask new questions and to see power dynamics and relationships that may otherwise be missed or misread. As a result, they have an important role to play in any action research with transformative intentions.
Big returns for a little more investment
Authors: Raymer Annalisa
Published: February 2009

Action researchers can effectively uncover the theory embedded within inquiries by using a combination of analysis approaches and heuristic models already widely known. Presented here is one approach for mapping theory to capture elements of both program theory and theory of practice. Using a case of a Participatory Evaluative Action Research (PEAR), the article demonstrates how data collected over the course of an inquiry can yield extra contributions, in addition to its original usages for informing local actions and decision-making.
Building emergent situated knowledges in participatory action research
Authors: Genat Bill
Published: February 2009

Participatory action research (PAR) draws theoretically on the concepts of symbolic interactionism, particularly with regard to the collaborative construction and production of meanings. This article describes how action research builds meaningful theory at the local level thereby enabling researchers, researcher-participants and their local partners to foreground shared local understandings to critique more dominant discourses and policy positions regarding their circumstances. In so doing, this approach to PAR also draws on feminist understandings of standpoint epistemologies and situated knowledges and aligns itself with the politics of post-colonial theory and decolonizing methodologies.
Final reflections, unanswered questions
Authors: Dick Bob , Stringer Ernie , Huxham Chris
Published: February 2009

The interest in theory is greater than we anticipated. However, in looking at the role of theory in action research, there are more questions than answers. With few exceptions, the way in which theory is built from experience remains elusive. How is it done? It seems that frameworks are useful in making sense of the world. But which frameworks? What do they leave out? How accessible are they to participants? What effect does that have on participation, and in turn on actions? These and other questions about theory may have to wait for other occasions.
Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions
Authors: Rocco Tonette S. , Plakhotnik Maria S.
Published: February 2009

This essay starts with a discussion of the literature review, theoretical framework, and conceptual framework as components of a manuscript. This discussion includes similarities and distinctions among these components and their relation to other sections of a manuscript such as the problem statement, discussion, and implications. The essay concludes with an overview of the literature review, theoretical framework, and conceptual framework as separate types of manuscripts. Understanding similarities and differences among the literature review, theoretical framework, and conceptual framework can help novice and experienced researchers in organizing, conceptualizing, and conducting their research, whether qualitative, quantitative, or mixed-methods.
Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions
Authors: Dobkin Bruce H.
Published: February 2009

Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions. Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions.
Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant
Authors: Mosnier Laurent O. , Zampolli Antonella , Kerschen Edward J. , Schuepbach Reto A. , Banerjee Yajnavalka , Fernández José A. , Yang Xia V. , Riewald Matthias , Weiler Hartmut , Ruggeri Zaverio M. , Griffin John H.
Published: February 2009

Activated protein C (APC) reduces mortality in severe sepsis patients. APC exerts anticoagulant activities via inactivation of factors Va and VIIIa and cytoprotective activities via endothelial protein C receptor and protease-activated receptor-1. APC mutants with selectively altered and opposite activity profiles, that is, greatly reduced anticoagulant activity or greatly reduced cytoprotective activities, are compared here. Glu149Ala-APC exhibited enhanced in vitro anticoagulant and in vivo antithrombotic activity, but greatly diminished in vitro cytoprotective effects and in vivo reduction of endotoxin-induced murine mortality. Thus, residue Glu149 and the C-terminal region of APC's light chain are identified as functionally important for expression of multiple APC activities. In contrast to Glu149Ala-APC, 5A-APC (Lys191-193Ala + Arg229/230Ala) with protease domain mutations lacked in vivo antithrombotic activity, although it was potent in reducing endotoxin-induced mortality, as previously shown. These data imply that APC molecular species with potent antithrombotic activity, but without robust cytoprotective activity, are not sufficient to reduce mortality in endotoxemia, emphasizing the need for APC's cytoprotective actions, but not anticoagulant actions, to reduce endotoxin-induced mortality. Protein engineering can provide APC mutants that permit definitive mechanism of action studies for APC's multiple activities, and may also provide safer and more effective second-generation APC mutants with reduced bleeding risk.
Quantitative measures for the management and comparison of annotated genomes
Authors: Eilbeck Karen , Moore Barry , Holt Carson , Yandell Mark
Published: February 2009

Background

The ever-increasing number of sequenced and annotated genomes has made management of their annotations a significant undertaking, especially for large eukaryotic genomes containing many thousands of genes. Typically, changes in gene and transcript numbers are used to summarize changes from release to release, but these measures say nothing about changes to individual annotations, nor do they provide any means to identify annotations in need of manual review.

Results

In response, we have developed a suite of quantitative measures to better characterize changes to a genome's annotations between releases, and to prioritize problematic annotations for manual review. We have applied these measures to the annotations of five eukaryotic genomes over multiple releases – H. sapiens, M. musculus, D. melanogaster, A. gambiae, and C. elegans.

Conclusion

Our results provide the first detailed, historical overview of how these genomes' annotations have changed over the years, and demonstrate the usefulness of these measures for genome annotation management.
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice
Authors: Prinzen Claudia , Trümbach Dietrich , Wurst Wolfgang , Endres Kristina , Postina Rolf , Fahrenholz Falk
Published: February 2009

Background

In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation, and alleviated cognitive deficits. Furthermore, ADAM10 overexpression increased the cortical synaptogenesis. These results suggest that upregulation of ADAM10 in the brain has beneficial effects on AD pathology.

Results

To assess the influence of ADAM10 on the gene expression profile in the brain, we performed a microarray analysis using RNA isolated from brains of five months old mice overexpressing either the α-secretase ADAM10, or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, in ADAM10 transgenic mice 355 genes, and in dnADAM10 mice 143 genes were found to be differentially expressed. A higher number of genes was differentially regulated in double-transgenic mouse strains additionally expressing the human APP[V717I]mutant.

Overexpression of proteolytically active ADAM10 affected several physiological pathways, such as cell communication, nervous system development, neuron projection as well as synaptic transmission. Although ADAM10 has been implicated in Notch and β-catenin signaling, no significant changes in the respective target genes were observed in adult ADAM10 transgenic mice.

Real-time RT-PCR confirmed a downregulation of genes coding for the inflammation-associated proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression. Overexpression of the dominant-negative form dnADAM10 led to a significant increase in the expression of the fatty acid-binding protein Fabp7, which also has been found in higher amounts in brains of Down syndrome patients.

Conclusion

In general, there was only a moderate alteration of gene expression in ADAM10 overexpressing mice. Genes coding for pro-inflammatory or pro-apoptotic proteins were not over-represented among differentially regulated genes. Even a decrease of inflammation markers was observed. These results are further supportive for the strategy to treat AD by increasing the α-secretase activity.
Genome-wide analysis of chicken snoRNAs provides unique implications for the evolution of vertebrate snoRNAs
Authors: Shao Peng , Yang Jian-Hua , Zhou Hui , Guan Dao-Gang , Qu Liang-Hu
Published: February 2009

Background

Small nucleolar RNAs (snoRNAs) represent one of the largest groups of functionally diverse trans-acting non-protein-coding (npc) RNAs currently known in eukaryotic cells. Chicken snoRNAs have been very poorly characterized when compared to other vertebrate snoRNAs. A genome-wide analysis of chicken snoRNAs is therefore of great importance to further understand the functional evolution of snoRNAs in vertebrates.

Results

Two hundred and one gene variants encoding 93 box C/D and 62 box H/ACA snoRNAs were identified in the chicken genome and are predicted to guide 86 2'-O-ribose methylations and 69 pseudouridylations of rRNAs and spliceosomal RNAs. Forty-four snoRNA clusters were grouped into four categories based on synteny characteristics of the clustered snoRNAs between chicken and human. Comparative analyses of chicken snoRNAs revealed extensive recombination and separation of guiding function, with cooperative evolution between the guiding duplexes and modification sites. The gas5-like snoRNA host gene appears to be a hotspot of snoRNA gene expansion in vertebrates. Our results suggest that the chicken is a good model for the prediction of functional snoRNAs, and that intragenic duplication and divergence might be the major driving forces responsible for expansion of novel snoRNA genes in the chicken genome.

Conclusion

We have provided a detailed catalog of chicken snoRNAs that aids in understanding snoRNA gene repertoire differences between avians and other vertebrates. Our genome-wide analysis of chicken snoRNAs improves annotation of the 'darkness matter' in the npcRNA world and provides a unique perspective into snoRNA evolution in vertebrates.
Genome-wide analysis of the PreA/PreB (QseB/QseC) regulon of Salmonella enterica serovar Typhimurium
Authors: Merighi Massimo , Septer Alecia N , Carroll-Portillo Amanda , Bhatiya Aditi , Porwollik Steffen , McClelland Michael , Gunn John S
Published: February 2009

Background

The Salmonella PreA/PreB two-component system (TCS) is an ortholog of the QseBC TCS of Escherichia coli. In both Salmonella and E. coli, this system has been shown to affect motility and virulence in response to quorum-sensing and hormonal signals, and to affect the transcription of the Salmonella enterica serovar Typhimurium (S. Typhimurium) pmrAB operon, which encodes an important virulence-associated TCS.

Results

To determine the PreA/PreB regulon in S. Typhimurium, we performed DNA microarrays comparing the wild type strain and various preA and/or preB mutants in the presence of ectopically expressed preA (qseB). These data confirmed our previous findings of the negative effect of PreB on PreA gene regulation and identified candidate PreA-regulated genes. A proportion of the activated loci were previously identified as PmrA-activated genes (yibD, pmrAB, cptA, etc.) or were genes located in the local region around preA, including the preAB operon. The transcriptional units were defined in this local region by RT-PCR, suggesting three PreA activated operons composed of preA-preB, mdaB-ygiN, and ygiW-STM3175. Several putative virulence-related phenotypes were examined for preAB mutants, resulting in the observation of a host cell invasion and slight virulence defect of a preAB mutant. Contrary to previous reports on this TCS, we were unable to show a PreA/PreB-dependent effect of the quorum-sensing signal AI-2 or of epinephrine on S. Typhimurium with regard to bacterial motility.

Conclusion

This work further characterizes this unorthadox OmpR/EnvZ class TCS and provides novel candidate regulated genes for further study. This first in-depth study of the PreA/PreB regulatory system phenotypes and regulation suggests significant comparative differences to the reported function of the orthologous QseB/QseC in E. coli.
Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells
Authors: Tan Yuliang , Zhang Bo , Wu Tao , Skogerbø Geir , Zhu Xiaopeng , Guo Xiangqian , He Shunmin , Chen Runsheng
Published: February 2009

Background

Small noncoding RNAs (ncRNAs), including short interfering RNAs (siRNAs) and microRNAs (miRNAs), can silence genes at the transcriptional, post-transcriptional or translational level [1, 2].

Results

Here, we show that microRNA-10a (miR-10a) targets a homologous DNA region in the promoter region of the hoxd4 gene and represses its expression at the transcriptional level. Mutational analysis of the miR-10a sequence revealed that the 3' end of the miRNA sequence is the most critical element for the silencing effect. MicroRNA-10a-induced transcriptional gene inhibition requires the presence of Dicer and Argonautes 1 and 3, and it is related to promoter associated noncoding RNAs. Bisulfite sequencing analysis showed that the reduced hoxd4 expression was accompanied by de novo DNA methylation at the hoxd4 promoter. We further demonstrated that trimethylation of histone 3 lysine 27 (H3K27me3) is involved in the miR-10a-induced hoxd4 transcriptional gene silence.

Conclusion

In conclusion, our results demonstrate that miR-10a can regulate human gene expression in a transcriptional manner, and indicate that endogenous small noncoding RNA-induced control of transcription may be a potential system for expressional regulation in human breast cancer cells.
Genetic correction of splice site mutation in purified and enriched myoblasts isolated from mdx5cv mice
Authors: Maguire Katie , Suzuki Takayuki , DiMatteo Darlise , Parekh-Olmedo Hetal , Kmiec Eric
Published: February 2009

Background

Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that results in the production of a dysfunctional form of the protein, dystrophin. The mdx5cv mouse is a model of DMD in which a point mutation in exon 10 of the dystrophin gene creates an artificial splice site. As a result, a 53 base pair deletion of exon 10 occurs with a coincident creation of a frameshift and a premature stop codon. Using primary myoblasts from mdx5cv mice, single-stranded DNA oligonucleotides were designed to correct this DNA mutation.

Results

Single-stranded DNA oligonucleotides that were designed to repair this splice site mutation corrected the mutation in the gene and restored expression of wild-type dystrophin. This repair was validated at the DNA, RNA and protein level. We also report that the frequency of genetic repair of the mdx mutation can be enhanced if RNAi is used to suppress expression of the recombinase inhibitor protein Msh2 in cultures containing myoblasts but not in those heavily enriched in myoblasts.

Conclusion

Exogenous manipulations, such as RNAi, are certainly feasible and possibly required to increase the successful application of gene repair in some primary or progenitor muscle cells.
CD133+adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF)
Authors: Carter Debra A , Dick Andrew D , Mayer Eric J
Published: February 2009

Background

CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF), sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres.

Methods

Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS) CD133+ retinal cells were enriched from post mortem adult human retina. CD133+ retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation.

Results

We demonstrated purification (to 95%) of CD133+ cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133+ retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133+ retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression) without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal.

Conclusion

These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.
Factors determining the outcome of children hospitalized with severe pneumonia
Authors: Tiewsoh Karalanglin , Lodha Rakesh , Pandey Ravindra M , Broor Shobha , Kalaivani M , Kabra Sushil K
Published: February 2009

Background

Pneumonia is one of the leading causes of morbidity and mortality in under fives. We carried out a comprehensive study to identify factors influencing both mortality and morbidity for children less than 5 years of age hospitalized with severe pneumonia.

Methods

200 hospitalized children aged 2–60 months with World Health Organization (WHO) defined severe pneumonia were enrolled in the study. The children were managed using a standard protocol. They were closely followed up for need for change in antibiotics, prolonged hospital stay, need for mechanical ventilation and mortality. Data on the factors influencing the outcome were collected.

Results

Of 200 children enrolled in the study, 113 (56.5%) needed a change in antibiotics, 102 (51%) stayed for more than 5 days in the hospital, 41 (20.5%) needed mechanical ventilation and 21 (10.5%) died. On multivariate analysis, lack of exclusive breastfeeding [RR (95%CI) 2.63 (2.16–2.86)], overcrowding [RR (95%CI) 1.94 (1.35–2.38)] and an abnormal chest x-ray [RR (95%CI) 2.29 (1.22–3.44)] were associated with the need for change of antibiotics. Lack of exclusive breastfeeding [RR (95%CI) 2.56 (2.0–2.93)], overcrowding [RR (95%CI) 2.59 (1.78–3.23)] and an abnormal chest x-ray [RR (95%CI) 2.99 (1.65–4.38)] were identified as determinants for prolonged hospital stay. Head nodding [RR (95%CI) 8.34 (2.71–12.77)], altered sensorium [RR (95%CI) 5.44 (1.34–17.56)], abnormal leukocyte counts [RR (95%CI) 5.85(1.36–17.14)] and pallor [RR (95%C) 10.88 (2.95–20.40)] were associated with mortality. Head nodding (RR (95% CI) 4.73 (1.50–6.36)] and cyanosis (RR (95%CI) 5.06 (1.80–11.34)] were the determining factors for mechanical ventilation.

In radiographically confirmed pneumonia, the determining factors for change of antibiotics were: lack of exclusive breast feeding [RR (95% CI) 2.05 (1.69–2.2)] and low birth weight [RR (95% CI) 1.59 (1.1–1.89)]. For prolonged hospital stay, the factors identified were mothers' education less than graduation [RR (95% CI) 1.5 (1.19–1.7)], lack of exclusive breast feeding [RR (95% CI) 1.77 (1.19–2.09)] and oxygen saturation of < 90% at time of presentation [RR (95% CI) 2.06 (1.42–2.42)]. Determinants for mechanical ventilation were mothers' education less than graduation [RR (95% CI) 3.6 (1.15–6.3)] and cyanosis at presentation [RR (95% CI) 10.9 (1.56–18.9)]. For mortality, the only determinant was pallor [RR (95% CI) 10.54 (1.8–21.79)].

Conclusion

Children hospitalized with severe community acquired pneumonia [as defined by World Health Organization (WHO)] who had not received exclusive breast feeding, had stayed in an overcrowded homes and had an abnormal chest radiograph were more likely to fail to respond with primary antibiotic regimen and require change of antibiotics and prolonged hospital stay.

In children with radiographically confirmed pneumonia, lack of breast feeding and low birth weight was associated with need for change in antibiotics.
Potential and Actual Terrestrial Rabies Exposures in People and Domestic Animals, Upstate South Carolina, 1994–2004: A Surveillance Study
Authors: Roseveare Catherine W , Goolsby W David , Foppa Ivo M
Published: February 2009

Background

Although there has been a reduction of rabies in pets and domestic animals during recent decades in the United States, rabies remains enzootic among bats and several species of terrestrial wildlife. Spillover transmission of wildlife rabies to domestic animals therefore remains a public health threat

Methods

Retrospective analysis of surveillance data of reported animal incidents (bites, scratches, mucous membrane contacts) from South Carolina, 1995 to 2003, was performed to assess risk factors of potential rabies exposures among human and animal victims.

Results

Dogs and cats contributed the majority (66.7% and 26.4%, respectively) of all reported incidents, with stray dogs and cats contributing 9.0% and 15.1 respectively. Current rabies vaccination status of dogs and cats (40.2% and 13.8%, respectively) were below World Health Organization recommended levels. Owned cats were half as likely to be vaccinated for rabies as dogs (OR 0.53, 95% CI 0.48, 0.58). Animal victims were primarily exposed to wildlife (83.0%), of which 27.5% were rabid. Almost 90% of confirmed rabies exposures were due to wildlife. Skunks had the highest prevalence of rabies among species of exposure animals (63.2%). Among rabid domestic animals, stray cats were the most commonly reported (47.4%).

Conclusion

While the majority of reported potential rabies exposures are associated with dog and cat incidents, most rabies exposures derive from rabid wildlife. Stray cats were most frequently rabid among domestic animals. Our results underscore the need for improvement of wildlife rabies control and the reduction of interactions of domestic animals, including cats, with wildlife.
Incorporating double copies of a chromatin insulator into lentiviral vectors results in less viral integrants
Authors: Nielsen Troels T , Jakobsson Johan , Rosenqvist Nina , Lundberg Cecilia
Published: February 2009

Background

Lentiviral vectors hold great promise as gene transfer vectors in gene therapeutic settings. However, problems related to the risk of insertional mutagenesis, transgene silencing and positional effects have stalled the use of such vectors in the clinic. Chromatin insulators are boundary elements that can prevent enhancer-promoter interactions, if placed between these elements, and protect transgene cassettes from silencing and positional effects. It has been suggested that insulators can improve the safety and performance of lentiviral vectors. Therefore insulators have been incorporated into lentiviral vectors in order to enhance their safety profile and improve transgene expression. Commonly such insulator vectors are produced at lower titers than control vectors thus limiting their potential use.

Results

In this study we cloned in tandem copies of the chicken β-globin insulator (cHS4) on both sides of the transgene cassette in order to enhance the insulating effect. Our insulator vectors were produced at significantly lower titers compared to control vectors, and we show that this reduction in titer is due to a block during the transduction process that appears after reverse transcription but before integration of the viral DNA. This non-integrated viral DNA could be detected by PCR and, importantly, prevented efficient transduction of target cells.

Conclusion

These results have importance for the future use of insulator sequences in lentiviral vectors and might limit the use of insulators in vectors for in vivo use. Therefore, a careful analysis of the optimal design must be performed before insulators are included into clinical lentiviral vectors.
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2)
Authors: Winger Jonathan A , Hantschel Oliver , Superti-Furga Giulio , Kuriyan John
Published: February 2009

Background

Imatinib represents the first in a class of drugs targeted against chronic myelogenous leukemia to enter the clinic, showing excellent efficacy and specificity for Abl, Kit, and PDGFR kinases. Recent screens carried out to find off-target proteins that bind to imatinib identified the oxidoreductase NQO2, a flavoprotein that is phosphorylated in a chronic myelogenous leukemia cell line.

Results

We examined the inhibition of NQO2 activity by the Abl kinase inhibitors imatinib, nilotinib, and dasatinib, and obtained IC50values of 80 nM, 380 nM, and >100 μM, respectively. Using electronic absorption spectroscopy, we show that imatinib binding results in a perturbation of the protein environment around the flavin prosthetic group in NQO2. We have determined the crystal structure of the complex of imatinib with human NQO2 at 1.75 Å resolution, which reveals that imatinib binds in the enzyme active site, adjacent to the flavin isoalloxazine ring. We find that phosphorylation of NQO2 has little effect on enzyme activity and is therefore likely to regulate other aspects of NQO2 function.

Conclusion

The structure of the imatinib-NQO2 complex demonstrates that imatinib inhibits NQO2 activity by competing with substrate for the active site. The overall conformation of imatinib when bound to NQO2 resembles the folded conformation observed in some kinase complexes. Interactions made by imatinib with residues at the rim of the active site provide an explanation for the binding selectivity of NQO2 for imatinib, nilotinib, and dasatinib. These interactions also provide a rationale for the lack of inhibition of the related oxidoreductase NQO1 by these compounds. Taken together, these studies provide insight into the mechanism of NQO2 inhibition by imatinib, with potential implications for drug design and treatment of chronic myelogenous leukemia in patients.
Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1
Authors: Parkinson Pamela F , Kannangara Timal S , Eadie Brennan D , Burgess Braydon L , Wellington Cheryl L , Christie Brian R
Published: February 2009

Background

Cognitive deficits are a hallmark feature of both Down Syndrome (DS) and Alzheimer's Disease (AD). Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of Aβ peptides. The ATP-Binding Cassette-G1 (ABCG1) transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis.

Results

To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1.

Conclusion

These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.
GO Explorer: A gene-ontology tool to aid in the interpretation of shotgun proteomics data
Authors: Carvalho Paulo C , Fischer Juliana SG , Chen Emily I , Domont Gilberto B , Carvalho Maria GC , Degrave Wim M , Yates John R , Barbosa Valmir C
Published: February 2009

Background

Spectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge.

Results

Here we present a new algorithm, termed GO Explorer (GOEx), that leverages the gene ontology (GO) to aid in the interpretation of proteomic data. GOEx stands out because it combines data from protein fold changes with GO over-representation statistics to help draw conclusions. Moreover, it is tightly integrated within the PatternLab for Proteomics project and, thus, lies within a complete computational environment that provides parsers and pattern recognition tools designed for spectral counting. GOEx offers three independent methods to query data: an interactive directed acyclic graph, a specialist mode where key words can be searched, and an automatic search. Its usefulness is demonstrated by applying it to help interpret the effects of perillyl alcohol, a natural chemotherapeutic agent, on glioblastoma multiform cell lines (A172). We used a new multi-surfactant shotgun proteomic strategy and identified more than 2600 proteins; GOEx pinpointed key sets of differentially expressed proteins related to cell cycle, alcohol catabolism, the Ras pathway, apoptosis, and stress response, to name a few.

Conclusion

GOEx facilitates organism-specific studies by leveraging GO and providing a rich graphical user interface. It is a simple to use tool, specialized for biologists who wish to analyze spectral counting data from shotgun proteomics. GOEx is available athttp://pcarvalho.com/patternlab.
Turkish version of impact on family scale: a study of reliability and validity
Authors: Bek Nilgun , Simsek I Engin , Erel Suat , Yakut Yavuz , Uygur Fatma
Published: February 2009

Background

Although there is a considerably high prevalence of developmental disorders in Turkey there are not many assessment tools related to evaluating the impact of these children on their family. The aim of this study was to determine the validity and reliability of the Turkish version of the Impact on Family Scale (IPFAM), a health related quality of life measurement to be utilized in clinical trials, health care services, research and evaluation.

Methods

Caregivers of 85 children with developmental disabilities answered the questionnaire and 65 of them answered it twice with a one week interval. The reliability of the measurement was assessed by Cronbach's alpha coefficient, and with intraclass correlation coefficient (ICC) for test-retest reliability. Construct validity was assessed by calculating the correlation between total impact score of IPFAM, WeeFIM and the physiotherapists' evaluation via Visual Analogue Scale (VAS) to determine the child's disability.

Results

Test-retest reliability was found to be ICC = 0.953 for total impact, 0.843 for financial support, 0.940 for general impact, 0.871 for disruption of social relations and 0.787 for coping. Internal consistency was tested using Cronbach's alpha and was found to be 0.902 for total impact of IPFAM. For construct validity the correlation between total impact score of IPFAM and WeeFIM was r = -0,532 (p < 0.001) and the correlation between total impact score of IPFAM and the physiotherapist's evaluation was r = 0.519 (p < 0.001).

Conclusion

The Turkish version of IPFAM was found to be a reliable and valid instrument for assessing the impact of developmental disorders of the child on the family.
Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth
Authors: Fletcher Helen A , Keyser Alana , Bowmaker Mark , Sayles Peter C , Kaplan Gilla , Hussey Greg , Hill Adrian VS , Hanekom Willem A
Published: February 2009

Background

Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult.

Methods

To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix® HumanRef-8 Expression BeadChip (Illumina) to measure expression of >16,000 genes.

Results

We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-γ, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated.

Conclusion

Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.
Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors
Authors: Frogne Thomas , Laenkholm Anne-Vibeke , Lyng Maria B , Henriksen Katrine Lütken , Lykkesfeldt Anne E
Published: February 2009

Introduction

High expression of total HER2 protein confers poor prognosis for breast cancer patients. HER2 is a member of the HER family consisting of four receptors, HER1 to HER4. HER receptor activity is regulated by a variety of mechanisms, and phosphorylation of the C-terminal part of the HER receptors is a marker for active signaling. The importance of phosphorylation and thereby activation of the HER1 to HER4 receptors, however, has not been investigated concomitantly in breast tumors. In the present study we examined the importance of active HER signaling in breast tumor biopsies and paired metastases, by evaluating the expression of phosphorylated HER1, HER2, HER3, Erk, Akt and the total level of HER4 and HER2.

Methods

Immunohistochemical analysis was performed on 268 primary breast tumors and 30 paired metastatic lesions from postmenopausal women with hormone receptor-positive breast tumors, who had received adjuvant tamoxifen therapy. The observed protein expression levels were analyzed for co-expression, for correlation to clinicopathological parameters and for prognostic value in relation to disease-free survival and overall survival. Lastly, the difference between protein levels in primary tumors versus metastasis was evaluated.

Results

In the primary tumors, 8%, 18%, 14% and 15% of cases were scored positive for total HER2, pHER1, pHER2 and pHER3 expression, respectively. HER4 was expressed with strong intensity in 68% and at moderate intensity in 29% of cases. The activated forms of Akt and Erk were quite uniformly expressed in the categories; negative, moderate or strong. In univariate analysis, expression of total HER2, pHER1, pHER2 and pHER3 was significantly associated with poor disease-free survival. Strong HER4 expression was associated with prolonged disease-free as well as with overall survival. Expression of pAkt and pErk was not correlated with survival. In multivariate analysis, pHER2 expression was clearly an independent marker for poor disease-free survival and overall survival when tested against tumor size, tumor grade, nodal status and HER2. Lastly, comparison of HER receptor expression in metastatic versus primary tumors showed a significant increase in expression of pHER1 and pHER3 in the metastases.

Conclusions

In hormone receptor-positive breast cancer, determination of pHER2 yields additional prognostic information about poor prognosis compared with the current clinical standard for measuring HER2.