bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Thermo-oxidative and Wear Stability of Black Berry Wood and Its Polymethylmethacrylate and Polyacrylonitrile Impregnated Wood Composites
Authors: Tyagi Y.K. , Sah P.L.
Published: December 2009

In this study, wood polymer composites (WPCs) were prepared with the impregnation of polymeric monomers methylmethacrylate (5.061 moles/L) and acrylonitrile (5.061 moles/L) into properly shaped black berry wood specimens in the presence of benzoyl peroxide (0.06 moles/L) to initiate the polymerization process forming free radicals in the benzene medium at 74 ± 1°C. Untreated wood and its polymethylmethacrylate (PMMA) and polyacrylonitrile impregnated wood composites were evaluated for stability of wood against thermo-oxidation in terms of differential thermogravimetry, thermogravimetry, differential thermal analysis in air, and wear stability in terms of wear volume. Such prepared WPCs indicated a significant improvement in all the properties investigated. It was also investigated that polyacrylonitrile impregnation imparted more resistance to wood against thermo-oxidation and wear in comparison to PMMA impregnation. Presence of PMMA and polyacrylonitrile impregnation into black berry wood was confirmed through scanning electron microscopy.
Influence of Nanoparticle Loading on Craze Formation and Crack Propagation of Polycarbonate in Different Environments
Authors: Zhou Rui-Juan , Burkhart Thomas
Published: December 2009

In the present work, the craze formation and crack propagation of nanosilica-filled polycarbonate (PC) in different environments were investigated by using a bent strip test with constant strain and a creep test with static constant stress. The result of bent strip test indicates that crazes or microcracks are formed more easily in isopropanol (IPA) than in air, and the number of crazes increases with increasing particle loading in the matrix. The following three-point bending test shows a clear decrease of flexural properties of samples prebent in IPA compared to samples prebent in air. By creep test under constant loading, the samples tested in toluene fail much earlier than those tested in IPA due to accelerated diffusion of toluene into PC matrix and subsequent formation of macrovoids. The incorporation of nanoparticles in PC significantly improves the lifetime of PC composites in chemical agents due to combined effects of nanoparticles.
Main Challenges for Cooperatives in Venezuela
Authors: Piñeiro Camila
Published: December 2009

A considerable number of Venezuelan cooperative members present serious deficiencies in administrative and technical skills, as well as motivation. Production cooperatives in that nation are also having great difficulty in competing with their capitalist counterparts for inputs and clients. Their dependency on state institutions for access to capital and sale contracts is also threatening their sustainability. This situation is aggravated because little integration exists among them. To overcome these challenges, Venezuelan cooperatives need to coordinate their activities among themselves and with neighboring communities. Such democratic planning or coordination would also serve to consolidate their organizational and ethical principles, and to transform them into true socialist enterprises that effectively and efficiently satisfy social needs
‘No matter what I did I would still end up in the same position’
Authors: Moore Sian
Published: December 2009

This article explores age as a factor defining the labour market experience of older women. Drawing upon work histories it argues that discrimination on the grounds of age is bound up with gender, race and class. Older women described how all three categories had structured their working lives, with occupational and sectoral segregation underpinning a legacy of disadvantage. Intersectionality provides a tool to explore the interaction of social divisions over the life course, in preference to those privileging the instability and diversity of social identities. Although the testimonies of older women underline the need to situate their experiences within a unified system characterized by capitalist economic relations. The research enables analysis of the workers perceptions of the changing nature of work and the way that age can be constructed in terms of advantage and disadvantage within specific occupations and sectors already defined in terms of gender and race.
Clinical associations with autoantibody reactivities to individual components of U1 small nuclear ribonucleoprotein
Authors: Kaneko Y. , Suwa A. , Hirakata M. , Ikeda Y. , Kuwana M.
Published: December 2009

The reactivities to individual U1 small nuclear ribonucleoprotein (snRNP) components and their relationship to clinical features in patients with anti-U1 snRNP antibodies were examined. We evaluated 114 patients with connective tissue disease whose sera were positive for anti-U1 snRNP antibodies, but negative for anti-Sm antibodies. Antibodies to the U1 snRNP polypeptides 70K, A, and C were detected using subunit-specific enzyme-linked immunosorbent assays and antibodies to U1 small nuclear RNA (snRNA) were identified by an immunoprecipitation assay using deproteinized HeLa cell extracts. The clinical features were retrospectively obtained by chart review and prospectively collected after study entry. The pattern of antibody reactivities to U1 snRNP components varied among patients. The frequency of anti-70K, anti-A, anti-C, and anti-U1 snRNA antibodies was 60%, 86%, 74%, and 46%, respectively. There was no relationship between each reactivity and the clinical findings, but the presence of reactivities to increasing numbers of U1 snRNP components was correlated with sclerodactyly, shortness of the sublingual frenulum, esophageal dysfunction, and a lack of persistent proteinurea (p < 0.05 for all comparisons). The detection of autoantibody reactivities to individual components of the U1 snRNP particle is potentially useful for predicting the clinical course in patients with connective tissue disease and anti-U1 snRNP antibodies. Lupus (2010) 19, 307—312.
Meeting the Complex Needs of the Health Care Team: Identification of Nurse—Team Communication Practices Perceived to Enhance Patient Outcomes
Authors: Propp Kathleen M. , Apker Julie , Zabava Ford Wendy S. , Wallace Nancy , Serbenski Michele , Hofmeister Nancee
Published: December 2009

Nurses occupy a central position in today’s increasingly collaborative health care teams that place a premium on quality patient care. In this study we examined critical team processes and identified specific nurse—team communication practices that were perceived by team members to enhance patient outcomes. Fifty patient-care team members were interviewed to uncover forms of nurse communication perceived to improve team performance. Using a grounded theory approach and constant comparative analysis, study findings reveal two critical processes nurses contribute to as the most central and consistent members of the health care team: ensuring quality decisions and promoting a synergistic team. Moreover, the findings reveal 15 specific nurse—team communication practices that comprise these processes, and thereby are theorized to improve patient outcomes.
Pharmacokinetics of vancomycin in adult cancer patients
Authors: Al-Kofide Hadeel , Zaghloul Iman , Al-Naim Lamya
Published: December 2009

Background and Objectives. Gram-positive infections are prevalent among cancer patients and vancomycin therapy is often initiated empirically. A typical vancomycin pharmacokinetics is observed in such patients. The aim of the study was to evaluate the pharmacokinetics of vancomycin in this patient population and compare it to that of normal population.

Method and Results. The pharmacokinetics of vancomycin was examined retrospectively in two groups of patients — 18 cancer patients (age 43.4 ± 22.1 years) and 13 patients without cancer (age 48.5 ± 20.2 years). Following the administration of intermittent intravenous infusion of 15 mg/kg of vancomycin, peak and trough vancomycin serum concentration were determined after the third dose or at steady state as per standard of care. Vancomycin data were analyzed according to a one-compartment open model. Pharmacokinetic parameters such as clearance (CL), volume of distribution (Vd), and K elimination (ke) were calculated. Both Vd and CL were significantly higher in the cancer group (Mean Vd was 70 ± 45 L in the cancer group and 31.1 ± 8.3 L in the noncancer group, p-value 0.002; CL mean was 110.1 ± 42 mL/min in the cancer group and 71.2 ± 22.2 mL/min in the noncancer group, p-value 0.005). There was no significant difference in K elimination and half-life (t1/2).

Conclusion. Cancer patients may require higher than usual dosing regimens to ensure optimal therapeutic concentrations, since vancomycin CL and Vd is significantly higher in these patients, a dosing schedule as high as 60 mg/kg/day may be needed for cancer patients.
Melanoma in multiple sclerosis treated with natalizumab: causal association or coincidence?
Authors: Bergamaschi Roberto , Montomoli Cristina
Published: December 2009

We report a relapsing—remitting multiple sclerosis patient who received monthly intravenous natalizumab. After the fifth dose, the patient had a change in a long-standing mole. Ten months later, the mole became ulcerative and was ablated. Histological examination identified a spreading melanoma reaching the lower dermis (Clark level IV). Considering that at the moment the incidence of melanoma is estimable as about 5 per 100,000 multiple sclerosis person-years treated with natalizumab, and that, in the general population, the incidence of melanoma per 100,000 person-years is more than 10, we may speculate that the occurrence of melanoma during natalizumab treatment in multiple sclerosis is purely a coincidence.
Critical perspectives on ‘consumer involvement’ in health research
Authors: Ward Paul R. , Thompson Jill , Barber Rosemary , Armitage Christopher J. , Boote Jonathan D. , Cooper Cindy L. , Jones Georgina L.
Published: December 2009

Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This article presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented. First, we explore the ‘know—do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Second, we focus on one of the reasons for this ‘know—do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers.
An overview of limb replantation
Authors: Sorensen Kristian , Allison Keith
Published: December 2009

This review aims to provide an overview of the complex topic of limb replantation. The historical developments in limb replantation are detailed and the technical considerations of this surgery are discussed. Specific concerns relating to limb replantation surgery such as total ischaemic time and the amputation level are considered. It is important for rehabilitation to be tailored to the individual and the level of the injury. Attempted upper limb replantation is advocated in most cases but lower limb replantation is rarer. Lower limb replantation may have successful outcomes provided careful selection of patients takes place. Future improvements in replantation surgery may be influenced by developments in limb allograft surgery and nerve regeneration. Despite varying outcomes following successful replantation surgery, patients generally prefer to retain their own limbs rather than have a prosthesis and this should be considered as part of the informed decision making process by clinicians.
‘Ontological insecurity’ and ‘terror management’
Authors: Van Marle Fenna , Maruna Shadd
Published: December 2009

In this article, we seek to clarify and develop the concept of ontological insecurity by linking it to the better developed, empirical literature on ‘terror management theory’ in social psychology. We argue that the understanding of both ontological insecurity and terror management can be improved through this overdue integration. In particular, merging these literatures can have important explanatory power when it comes to understanding punitive attitudes. The considerable body of empirical evidence that has been gathered to validate the proposition behind terror management theory can be understood as providing indirect support for the concept of ontological insecurity on an individual level. On the other hand, the macrosociological research on ontological insecurity provides the largely decontextualized, laboratory-based literature on terror management with a well-developed understanding of why ‘terror management’ has become increasingly important in late modern society.
‘We/YouTube’: exploring sign-making in video-interaction
Authors: Adami Elisabetta
Published: December 2009

On the video-sharing website YouTube, the ‘video response’ option triggers a new interaction practice, i.e. communication threads started by an initial video, built up by video responses and resumed by a video-summary. This article examines a video-thread that starts from one of YouTube’s ‘most responded’ videos; by using a social semiotic multimodal analysis, the author investigates how video responses relate to the initial video and how the video-summary selectively transforms the resources of the responses while presenting itself as a resume of the video-thread. This analysis helps to explore the notion of ‘interest’, which shapes sign-making in a chain of semiosis in video-interaction, thus creating an approach to communication in which traditional notions of coherence and relevance are reshaped in terms of an interest-driven prompt—response relation.
Communicating emotion with animated text
Authors: Malik Sabrina , Aitken Jonathan , Waalen Judith Kelly
Published: December 2009

Traditionally, typographers and designers have relied on variations in the shape and form of letters and text to enhance textual meaning. It is hypothesized that animated text may be used to recreate a broader range of paralinguistic meaning and emotion than is possible with the use of static text alone. This pilot study was conducted to provide conceptual validation for the hypothesis that animated text can communicate certain emotions such as anger, sadness, happiness and fear. Animations were subjected to pre-testing and refined as needed. Subjects were tested for their understanding of the emotional content of a sample set of animated sentences. There was strong support for the animations created to measure ‘sadness’ and ‘happiness’. Findings also indicated that certain textual motions are associated with the intensity of certain emotions.
Tutorial on methods for interval-censored data and their implementation in R
Authors: Gómez Guadalupe , Calle M Luz , Oller Ramon , Langohr Klaus
Published: December 2009

Interval censoring is encountered in many practical situations when the event of interest cannot be observed and it is only known to have occurred within a time window. The theory for the analysis of interval-censored data has been developed over the past three decades and several reviews have been written. However, it is still a common practice in medical and reliability studies to simplify the interval censoring structure of the data into a more standard right censoring situation by, for instance, imputing the midpoint of the censoring interval. The availability of software for right censoring might well be the main reason for this simplifying practice. In contrast, several methods have been developed to deal with interval-censored data and the corresponding algorithms to make the procedures feasible are scattered across the statistical software or remain behind the personal computers of many researchers. The purpose of this tutorial is to present, in a pedagogical and unified manner, the methodology and the available software for analyzing interval-censored data. The paper covers frequentist non-parametric, parametric and semiparametric estimating approaches, non-parametric tests for comparing survival curves and a section on simulation of interval-censored data. The methods and the software are described using the data from a dental study.
The regression analysis of correlated interval-censored data
Authors: Komárek Arnošt , Lesaffre Emmanuel
Published: December 2009

The accelerated failure time (AFT) model is a useful alternative to the proportional hazard model for modelling interval-censored survival times. We illustrate the usefulness of a class of flexible AFT models. Flexibility is achieved by assuming that the distributional parts consist of penalized Gaussian mixtures. The AFT models are introduced and exemplified via research questions originating from a longitudinal dental study conducted in Flanders (North of Belgium). Emphasis is put on the analyzes which are performed using routines written in the R-language. They show the practical usefulness of our approach.
Linear transformation models for interval-censored data
Authors: Zhang Zhigang
Published: December 2009

In statistical analysis, when the value of a random variable is only known to be between two bounds, we say that this random variable is interval censored. This complicated censoring pattern is a common problem in research fields such as clinical trials or actuarial studies and raises challenges for statistical analysis. In this paper, we focus on regression analysis of case 2 interval-censored data. We first briefly review existing regression methods and an estimation approach under the class of linear transformation models developed by Zhang et al. We then propose a method for survival probability prediction via generalized estimating equations. We also consider a graphical model checking technique and a model selection tool. Some theoretical properties are established and the performance of our procedures is evaluated and illustrated by numerical studies including a real-life data analysis.
Screening for coeliac disease in an adult cohort of patients with type 1 diabetes
Authors: Waldron-Lynch Frank , Egan Aoife , Dunne Fidelma
Published: December 2009

Patients with type 1 diabetes have an increased prevalence of coeliac disease as compared with the general population due to common genotypes. Recent evidence has suggested that deregulation of gastrointestinal mucosal immunity may be essential to the development of both diseases. Currently, strong evidence supports the serological screening of paediatric patients with type 1 diabetes for coeliac disease. A key clinical question in the management of type 1 diabetes is whether adult patients should be routinely screened for coeliac disease. To investigate the use of coeliac screening in endocrine practice we retrospectively reviewed the records of 4,138 patients attending our diabetes centre over a four-year period and identified 572 patients with type 1 diabetes. We found that approximately one out of five patients with type 1 diabetes had been serologically screened for coeliac disease. The prevalence of coeliac disease at 1.69% in this adult cohort was lower than expected. This demonstrates that a significant proportion of adult patients with type 1 diabetes had been serologically screened for coeliac disease as part of routine care despite there being no clear indication to test.
Review: Metabolic memory in type 1 diabetes
Authors: Wright Alex D
Published: December 2009

Metabolic memory and its possible mechanisms are reviewed. In clinical practice in type 1 diabetes the concept of metabolic memory has developed largely from the observations of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, which followed the Diabetes Control and Complications Trial (DCCT). In the former intensive treatment group, after 10 years follow-up, when glycated haemoglobin levels had converged completely, there was less progression of retinopathy and lower rates of proliferative retinopathy. Diabetic nephropathy and neuropathy were similarly reduced. The combined DCCT and EDIC studies showed a reduction in the risk of any cardiovascular disease. Good early metabolic control affects outcome for at least 10 years and it is hoped this information can be translated into clinical practice to reduce significantly the burden of long-term complications.
Structured education in type 1 diabetes
Authors: Heller Simon R
Published: December 2009

The UK has been slow to promote effective intensive insulin therapy among those with type 1 diabetes. Although many adults use multiple injections, few self-manage their diabetes effectively and maintain tight glucose targets. However, in recent years reports from other countries that high-quality skills training in self- management can improve glycaemic control while lowering rates of hypoglycaemia have changed attitudes. The DAFNE (Dose Adjustment for Normal Eating) trial, which promotes a flexible approach to eating while maintaining tight glucose targets, demonstrated that patients require training to manage their diabetes successfully. Many centres now offer DAFNE, or similar structured education programmes, to adults with type 1 diabetes. Most patients have difficulty in sustaining the approach and the most appropriate ways of continuing support are unclear. A large number of units still provide no structured training depriving their patients of an essential component of their treatment. Formal diabetes education can no longer be regarded as an optional extra. It needs to be seen as essential to treatment as medication and therefore resourced, researched, evaluated and quality assured to a similar standard.
The Quest for the Cinematic Jesus: Scholarly Explorations in Jesus Films
Authors: Nguyen V. Henry T.
Published: December 2009

This article looks at an emerging research trend in biblical studies: Jesus and film. Within the past two decades, New Testament scholars have been attracted to the numerous films about Jesus not merely as a source of illustrations, but as an avenue to interpret the New Testament Gospels—or as Larry Kreitzer proposes, ‘reversing the hermeneutical flow’. With a growing interest in this new discipline to the task of biblical interpretation, it has become an accepted critical approach to the study of Jesus and the Gospels. This article surveys some various ways in which scholars have explored Jesus films, such as with a view to provide refreshing insights into difficult scholarly issues (e.g. the Synoptic problem). Furthermore, the article examines how scholars have begun in recent years to function as critics of controversial Jesus films and also as consultants for new film projects.
Graeco-Roman Religion in the Roman Empire: Old Assumptions and New Approaches
Authors: Rives James B.
Published: December 2009

This article surveys recent trends in research on Graeco-Roman religion, focusing on the first and second centuries CE. In the first half, I assess current views on what I call the old ‘master narrative’ of Graeco-Roman religious history in this period, that is, the assumption that the decline of traditional Graeco-Roman religion left a void filled on the one hand by the purely political phenomenon of imperial cult and on the other by mystery/oriental religions, which met the emotional needs of the populace. In the second half I discuss two areas of interest that have come to the fore in the wake of the old master narrative’s collapse: an approach to interpreting traditional Graeco-Roman religion that some scholars have termed the ‘ polis -religion model’, and a focus on religious life in the provinces of the Roman empire. As an appendix I include a brief survey of available scholarly resources in this field.
The Roman Imperial Cult and Revelation
Authors: Naylor Michael
Published: December 2009

The question of the relationship of the Roman Imperial Cult and Revelation has occupied the attention of scholars throughout the past one hundred years. During this time, major shifts have taken place both in the assessment of the Roman Imperial Cult in the context of the Roman Empire and in the interpretation of its role with respect to the book of Revelation. This article surveys and assesses these trends. It begins with a discussion of studies on the Roman Imperial Cult from the standpoint of classical studies. Next, texts within Revelation typically cited as indicating a response to emperor worship are introduced. The third and final section focuses upon studies on Revelation, with particular focus given to interpretive approaches, Christology, and the question of persecution under Domitian.
Deficits Underlying Impaired Visually Triggered Step Adjustments in Mildly Affected Stroke Patients
Authors: Nonnekes Jorik H. , Talelli Penny , de Niet Mark , Reynolds Raymond F. , Weerdesteyn Vivian , Day Brian L.
Published: December 2009

Background. The ability to make step adjustments while walking is often impaired following a stroke, but the basic sensorimotor control deficits responsible have not been established. Objective. To identify these deficits in Patients who have recovered from stroke leaving only mild lower limb impairment. Methods. Ten stroke and 10 age-matched control patients stepped onto an illuminated rectangle. In 40% of trials it jumped 140 mm either medially or laterally when the stepping foot left the ground, thus provoking a mid-step adjustment. In a separate block, patients performed the same task but with the body supported by a frame to eliminate balance responses. Results. Irrespective of support condition stroke patients produced short-latency foot trajectory adjustments compatible with a fast-acting, possibly subcortical, visuomotor process. However, the latency was slightly but significantly longer for the contralesional leg (148 ms) than the ipsilesional leg (141 ms) and longer than for controls (129 ms). Stroke patients’ foot adjustments were executed slower and undershot the target more than controls. These deficits were most pronounced in the medial direction when the body was unsupported. The pattern of undershooting was the same for ipsilesional and contralesional legs. Conclusions. Mildly impaired stroke patients have deficits in initiating and executing visually triggered step adjustments but more profound difficulties with balance control during the adjustment, which caused them to suppress mid-step adjustments of foot placement in the medial direction where balance demands were greatest. Paradoxically, such suppression outside the laboratory may also threaten balance if it leads to unsafe foot placement or obstacle collision.
Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster
Authors: Solovieff Nadia , Milton Jacqueline N. , Hartley Stephen W. , Sherva Richard , Sebastiani Paola , Dworkis Daniel A. , Klings Elizabeth S. , Farrer Lindsay A. , Garrett Melanie E. , Ashley-Koch Allison , Telen Marilyn J. , Fucharoen Supan , Ha Shau Yin , Li Chi-Kong , Chui David H. K. , Baldwin Clinton T. , Steinberg Martin H.
Published: December 2009

In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression.
Global transcriptional response after exposure of fission yeast cells to ultraviolet light
Authors: Skjølberg Henriette C , Fensgård Øyvind , Nilsen Hilde , Grallert Beáta , Boye Erik
Published: December 2009

Background

In many cell types, including the fission yeastSchizosaccharomyces pombe, a set of checkpoints are induced by perturbations of the cell cycle or by DNA damage. Many of the checkpoint responses include a substantial change of the transcriptional pattern. As part of characterising a novel G1/S checkpoint in fission yeast we have investigated whether a transcriptional response is induced after irradiation with ultraviolet light.

Results

Microarray analyses were used to measure the global transcription levels of all open reading frames of fission yeast after 254 nm ultraviolet irradiation, which is known to induce a G1/S checkpoint. We discovered a surprisingly weak transcriptional response, which is quite unlike the marked changes detected after some other types of treatment and in several other checkpoints. Interestingly, the alterations in gene expression after ultraviolet irradiation were not similar to those observed after ionising radiation or oxidative stress. Pathway analysis suggests that there is little systematic transcriptional response to the irradiation by ultraviolet light, but a marked, coordinated transcriptional response was noted on progression of the cells from G1 to S phase.

Conclusion

There is little response in fission yeast to ultraviolet light at the transcriptional level. Amongst the genes induced or repressed after ultraviolet irradiation we found none that are likely to be involved in the G1/S checkpoint mechanism, suggesting that the checkpoint is not dependent upon transcriptional regulation.
Evidence that phosphatidylinositol 3-kinase is involved in sperm-induced tyrosine kinase signaling in Xenopus egg fertilization
Authors: Mammadova Gunay , Iwasaki Tetsushi , Tokmakov Alexander A , Fukami Yasuo , Sato Ken-ichi
Published: December 2009

Background

Studies have examined the function of PI 3-kinase in the early developmental processes that operate in oocytes or early embryos of various species. However, the roles of egg-associated PI 3-kinase and Akt, especially in signal transduction at fertilization, are not well understood.

Results

Here we show that in Xenopus eggs, a potent inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), LY294002 inhibits sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization. LY294002 also inhibits sperm-induced dephosphorylation of mitogen-activated protein kinase, breakdown of cyclin B2 and Mos, and first embryonic cleavage, all of which are events of Ca2+-dependent egg activation. In fertilized eggs, an 85-kDa subunit of PI 3-kinase (p85) undergoes a transient translocation to the low-density, detergent-insoluble membranes (membrane microdomains) where Src tyrosine kinase signaling is operating. However, the tyrosine phosphorylation of p85 in fertilized eggs is not as evident as that in H2O2-activated eggs, arguing against the possibility that PI 3-kinase is activated by Src phosphorylation. Nevertheless, sperm-induced activation of PI 3-kinase has been demonstrated by the finding that Akt, a serine/threonine-specific protein kinase, is phosphorylated at threonine-308. The threonine-phosphorylated Akt also localizes to the membrane microdomains of fertilized eggs. Application of bp(V), an inhibitor of PTEN that dephosphorylates PIP3, the enzymatic product of PI 3-kinase, promotes parthenogenetic activation of Xenopus eggs. In vitro kinase assays demonstrate that PIP3 activates Src in a dose-dependent manner.

Conclusions

These results suggest that PI 3-kinase is involved in sperm-induced egg activation via production of PIP3 that would act as a positive regulator of the Src signaling pathway in Xenopus fertilization.
Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers
Authors: Krogius-Kurikka Lotta , Lyra Anna , Malinen Erja , Aarnikunnas Johannes , Tuimala Jarno , Paulin Lars , Mäkivuokko Harri , Kajander Kajsa , Palva Airi
Published: December 2009

Background

A growing amount of scientific evidence suggests that microbes are involved in the aetiology of irritable bowel syndrome (IBS), and the gastrointestinal (GI) microbiota of individuals suffering from diarrhoea-predominant IBS (IBS-D) is distinguishable from other IBS-subtypes. In our study, the GI microbiota of IBS-D patients was evaluated and compared with healthy controls (HC) by using a high-resolution sequencing method. The method allowed microbial community analysis on all levels of microbial genomic guanine plus cytosine (G+C) content, including high G+C bacteria.

Methods

The collective faecal microbiota composition of ten IBS-D patients was analysed by examining sequences obtained using percent G+C (%G+C) -based profiling and fractioning combined with 16S rRNA gene clone library sequencing of 3267 clones. The IBS-D library was compared with an analogous healthy-control library of 23 subjects. Real-time PCR analysis was used to identify phylotypes belonging to the class Gammaproteobacteria and the order Coriobacteriales.

Results

Significant differences were found between clone libraries of IBS-D patients and controls. The microbial communities of IBS-D patients were enriched in Proteobacteria and Firmicutes, but reduced in the number of Actinobacteria and Bacteroidetes compared to control. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutes were in greater abundance in the IBS-D clone library.

Conclusions

In the microbiota of IBS-D sufferers, notable differences were detected among the prominent bacterial phyla (Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria) localized within the GI tract.
Early severe morbidity and resource utilization in South African adults on antiretroviral therapy
Authors: de Cherif Teresa K Smith , Schoeman Jan H , Cleary Susan , Meintjes Graeme A , Rebe Kevin , Maartens Gary
Published: December 2009

Background

High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART). There is limited data on the causes of early morbidity on HAART and the associated resource utilization.

Methods

A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective.

Results

There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months). Median baseline CD4 count in the HAART group was 57 × 106cells/L (IQR 15-115). The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p < 0.001 and 39% versus 63%; p = 0.005 respectively). Immune reconstitution inflammatory syndrome was the primary reason for admission in 10% of the HAART group. Lengths of hospital stay per admission and inpatient survival were not significantly different between the two groups. Five of the 15 deaths in the HAART group were due to IRIS or adverse drug reactions. Median costs per admission of diagnostic and therapeutic services (laboratory investigations, radiology, intravenous fluids and blood, and non-ART medications) were higher in the HAART group compared with the no-HAART group (US$190 versus US$111; p = 0.001), but the more expensive non-curative costs (overhead, capital, and clinical staff) were not significantly different (US$1199 versus US$1128; p = 0.525).

Conclusions

Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services.
The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population
Authors: Li Hui , Wang Cheng-Ye , Wang Jia-Xin , Tang Nelson Leung-Sang , Xie Liang , Gong Yuan-Ying , Yang Zhao , Xu Liang-You , Kong Qing-Peng , Zhang Ya-Ping
Published: December 2009

Background

DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span.

Methods

Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel.

Results

A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions.

Conclusions

Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.
Rapid detection of SMARCB1 sequence variation using high resolution melting
Authors: Dagar Vinod , Chow Chung-Wo , Ashley David M , Algar Elizabeth M
Published: December 2009

Background

Rhabdoid tumors are rare cancers of early childhood arising in the kidney, central nervous system and other organs. The majority are caused by somatic inactivating mutations or deletions affecting the tumor suppressor locus SMARCB1 [OMIM 601607]. Germ-line SMARCB1 inactivation has been reported in association with rhabdoid tumor, epitheloid sarcoma and familial schwannomatosis, underscoring the importance of accurate mutation screening to ascertain recurrence and transmission risks. We describe a rapid and sensitive diagnostic screening method, using high resolution melting (HRM), for detecting sequence variations in SMARCB1.

Methods

Amplicons, encompassing the nine coding exons of SMARCB1, flanking splice site sequences and the 5' and 3' UTR, were screened by both HRM and direct DNA sequencing to establish the reliability of HRM as a primary mutation screening tool. Reaction conditions were optimized with commercially available HRM mixes.

Results

The false negative rate for detecting sequence variants by HRM in our sample series was zero. Nine amplicons out of a total of 140 (6.4%) showed variant melt profiles that were subsequently shown to be false positive. Overall nine distinct pathogenic SMARCB1 mutations were identified in a total of 19 possible rhabdoid tumors. Two tumors had two distinct mutations and two harbored SMARCB1 deletion. Other mutations were nonsense or frame-shifts. The detection sensitivity of the HRM screening method was influenced by both sequence context and specific nucleotide change and varied from 1: 4 to 1:1000 (variant to wild-type DNA). A novel method involving digital HRM, followed by re-sequencing, was used to confirm mutations in tumor specimens containing associated normal tissue.

Conclusions

This is the first report describing SMARCB1 mutation screening using HRM. HRM is a rapid, sensitive and inexpensive screening technology that is likely to be widely adopted in diagnostic laboratories to facilitate whole gene mutation screening.
Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma
Authors: Moen Ingrid , Tronstad Karl J , Kolmannskog Odd , Salvesen Gerd S , Reed Rolf K , Stuhr Linda EB
Published: December 2009

Background

Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen) has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil) into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix.

Methods

One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO) treatment (2 bar, pO2= 2 bar, 4 exposures à 90 min), whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO2= 0.2 bar) served as controls. Three doses of 5FU were tested for dose response. Uptake of [3H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif), collagen content, oxygen stress (measured as malondialdehyd levels), lymphatics and transcapillary transport in the tumors.

Results

The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%), but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor Pifand collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake.

Conclusion

We showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumorsper se, independently of changes in Pif, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO2.
Proteomic analysis during larval development and metamorphosis of the spionid polychaete Pseudopolydora vexillosa
Authors: Mok Flora SY , Thiyagarajan Vengatesen , Qian Pei-Yuan
Published: December 2009

Background

While the larval-juvenile transition (metamorphosis) in the spionid polychaete Pseudopolydora vexillosa involves gradual morphological changes and does not require substantial development of juvenile organs, the opposite occurs in the barnacle Balanus amphitrite. We hypothesized that the proteome changes during metamorphosis in the spionids are less drastic than that in the barnacles. To test this, proteomes of pre-competent larvae, competent larvae (ready to metamorphose), and juveniles of P. vexillosa were compared using 2-dimensional gel electrophoresis (2-DE), and they were then compared to those of the barnacle.

Results

Unlike the significant changes found during barnacle metamorphosis, proteomes of competent P. vexillosa larvae were more similar to those of their juveniles. Pre-competent larvae had significantly fewer protein spots (384 spots), while both competent larvae and juveniles expressed about 660 protein spots each. Proteins up-regulated during competence identified by MALDI-TOF/TOF analysis included a molecular chaperon (calreticulin), a signal transduction regulator (tyrosin activation protein), and a tissue-remodeling enzyme (metallopeptidase).

Conclusions

This was the first time to study the protein expression patterns during the metamorphosis of a marine polychaete and to compare the proteomes of marine invertebrates that have different levels of morphological changes during metamorphosis. The findings provide promising initial steps towards the development of a proteome database for marine invertebrate metamorphosis, thus deciphering the possible mechanisms underlying larval metamorphosis in non-model marine organisms.
T-cell activation promotes tumorigenesis in inflammation-associated cancer
Authors: Rauch Dan , Gross Shimon , Harding John , Bokhari Sirosh , Niewiesk Stefan , Lairmore Michael , Piwnica-Worms David , Ratner Lee
Published: December 2009

Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR) transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR-CD16+LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesisin vivo.