bluuebunny/crossref_metadata_2025 huggingface dataset:
Do 18-Month-Olds Really Attribute Mental States to Others?
Authors: Senju Atsushi , Southgate Victoria , Snape Charlotte , Leonard Mark , Csibra Gergely
Published: June 2011

In the research reported here, we investigated whether 18-month-olds would use their own past experience of visual access to attribute perception and consequent beliefs to other people. Infants in this study wore either opaque blindfolds (opaque condition) or trick blindfolds that looked opaque but were actually transparent (trick condition). Then both groups of infants observed an actor wearing one of the same blindfolds that they themselves had experienced, while a puppet removed an object from its location. Anticipatory eye movements revealed that infants who had experienced opaque blindfolds expected the actor to behave in accordance with a false belief about the object’s location, but that infants who had experienced trick blindfolds did not exhibit that expectation. Our results suggest that 18-month-olds used self-experience with the blindfolds to assess the actor’s visual access and to update her belief state accordingly. These data constitute compelling evidence that 18-month-olds infer perceptual access and appreciate its causal role in altering the epistemic states of other people.
Opt-out HIV testing: An ethical analysis of women’s reproductive rights
Authors: Fields Loren , Kaplan Clair
Published: June 2011

As the HIV epidemic continues to grow worldwide, women are increasingly and disproportionally affected. With the introduction of anti-retroviral medications that have been found to effectively prevent perinatal transmission of HIV, the approach to HIV testing in pregnant women has grown increasingly more controversial. In recent years, the model of voluntary counseling and testing (VCT) has come into question with opt-out testing now advocated for by the Centers for Disease Control and occurring widely in pregnancy. The benefits of opt-out testing are numerous and may justify its use in replacing the VCT that many have come to see as insufficient. An ethical analysis of opt-out testing suggests it may be at odds with true informed consent and involve a degree of coercion that would not be allowed outside the prenatal setting. If opt-out testing is going to remain the standard of care then the ethical issues it raises must be made transparent. Strategies need to be designed for ensuring that HIV counseling and testing in pregnancy is done in accordance with ethical and reproductive rights principles.
Compassion in care: A qualitative study of older people with a chronic disease and nurses
Authors: van der Cingel Margreet
Published: June 2011

This article describes compassion as perceived within the relationship between nurses and older persons with a chronic disease. The aim of the study is to understand the benefit of compassion for nursing practice within the context of long-term care. The design of the study involves a qualitative analysis of in-depth interviews with nurses and patients in three different care-settings. Results show the nature of compassion in seven dimensions: attentiveness, listening, confronting, involvement, helping, presence and understanding. Analysis of the data also shows in what way opinions of participants relate to issues raised in a previous literature study, for example the difference between pity and compassion. The conclusion states that compassion is a valuable process which motivates patients as well as nurses to cooperate in achieving relevant outcomes of care. The discussion involves some methodological issues. For one thing, further confirmation of the dimensions found is recommended.
A problem with inclusion in learning disability research
Authors: McClimens Alex , Allmark Peter
Published: June 2011

People with severe learning disability are particularly difficult to include in the research process. As a result, researchers may be tempted to focus on those with learning disability who can be included. The problem is exacerbated in this field as the political agenda of inclusion and involvement is driven by those people with learning disability who are the higher functioning. To overcome this we should first detach the notion of consent from ideas about autonomy and think instead of it as a way to avoid wronging others; this fits the original historical use of consent in research. This allows us to think in terms of including participants to the best of their abilities rather than in terms of a threshold of autonomy. Researchers could then use imaginative ways to include the least able and to ensure they are not wronged in research or by exclusion from it.
Broadening the Mind? Australian Student Reflections on the Experience of Overseas Study
Authors: Forsey Martin , Broomhall Susan , Davis Jane
Published: June 2011

Internationalization of higher education is usually accompanied by rhetorical flourishes that are always going to be difficult to live up to. The research reported here is based on surveys and focus group interviews with students at our home university that asks what students expect to learn and really learn from the university study abroad program. In emphasizing what the students surveyed and interviewed for this study reported learning, or thought they might learn, we are able to offer suggestions that can narrow the breach between the rhetoric and the practice of international education and suggest ways of ensuring that students gain as much as possible from their experiences while studying abroad.
Evaluation of Green Dot: An Active Bystander Intervention to Reduce Sexual Violence on College Campuses
Authors: Coker Ann L. , Cook-Craig Patricia G. , Williams Corrine M. , Fisher Bonnie S. , Clear Emily R. , Garcia Lisandra S. , Hegge Lea M.
Published: June 2011

Using a cross-sectional survey of a random sample of 7,945 college undergraduates, we report on the association between having received Green Dot active bystander behavior training and the frequency of actual and observed self-reported active bystander behaviors as well as violence acceptance norms. Of 2,504 students aged 18 to 26 who completed the survey, 46% had heard a Green Dot speech on campus, and 14% had received active bystander training during the past 2 years. Trained students had significantly lower rape myth acceptance scores than did students with no training. Trained students also reported engaging in significantly more bystander behaviors and observing more self-reported active bystander behaviors when compared with nontrained students. When comparing self-reported active bystander behavior scores of students trained with students hearing a Green Dot speech alone, the training was associated with significantly higher active bystander behavior scores. Those receiving bystander training appeared to report more active bystander behaviors than those simply hearing a Green Dot speech, and both intervention groups reported more observed and active bystander behaviors than nonexposed students.
Comparison of the 2- and 6-minute walk test in multiple sclerosis
Authors: Gijbels D , Eijnde BO , Feys P
Published: June 2011

The 6-minute walk test (6MWT) is often used to assess walking distance in multiple sclerosis (MS), but can be both time consuming for the investigator and exhausting for people with MS (pwMS). The present report compared the 6MWT scores of 40 ambulatory pwMS with their scores on the shorter 2-minute walk test (2MWT). The 2MWT estimated the 6MWT results with a mean relative error of 5% ( R2 = 0.96; p < 0.01). As the last 4-minute period of the 6MWT seems redundant, the 2MWT may be considered as a practical replacement for the 6MWT in routine clinical assessment.
Host selling in cyberspace: Product personalities and character advertising on popular children’s websites
Authors: Bucy Erik Page , Kim Sojung Claire , Park Miyeong Cecilia
Published: June 2011

This study examines the extent to which character advertising and other host-selling practices prevail on popular children’s websites and assesses whether commercial sites geared toward young users are complying with voluntary guidelines calling for a clear separation between advertising and content. A longitudinal analysis of 101 of the most popular children’s websites over a six-year period (2003, 2006 and 2009) found the integration of content and advertising through the use of spokescharacters, advergaming, and product personalities to be common. A majority of sites employed characters in their online advertising and most did not identify advertising with an explicit label when characters were featured on their homepages. A similar pattern was found for product-based games that featured spokescharacters. Branded sites with a recognizable product were much more likely to employ spokescharacters in product-based games than non-branded sites, and to use popular characters in their advertising. Over time, fewer websites featured product characters on their home pages, while the use of character advertising in product-based games inside websites increased substantially.
Multimodality, multisensoriality and ethnographic knowing: social semiotics and the phenomenology of perception
Authors: Pink Sarah
Published: June 2011

In this article I consider the potential for combining multimodality and anthropologically informed sensory ethnographic methodologies. I focus on a comparison between anthropological and multimodality approaches to the senses, the relationships between images and words, and ethnography. In doing so I reveal some of the tensions and fundamental differences between these approaches before then considering if and/or how these might be reconciled.
In-between practice: working in the ‘thirdspace’ of sensory and multimodal methodology
Authors: Hurdley Rachel , Dicks Bella
Published: June 2011

This article discusses how emergent sensory and multimodal methodologies can work in interaction to produce innovative social enquiry. A juxtaposition of two research projects — an ethnography of corridors and a mixed methods study of multimodal authoring and ‘reading’ practices — opened up this encounter. Sensory ethnography within social research methods aims to create empathetic, experiential ways of knowing participants’ and researchers’ worlds. The linguistic field of multimodality offers a rather different framework for research attending to the visual, material and acoustic textures of participants’ interactions. While both these approaches address the multidimensional character of social worlds, the ‘sensory turn’ centres the sensuous, bodied person — participant, researcher and audience/reader — as the ‘place’ for intimate, affective forms of knowing. In contrast, multimodal knowledge production is premised on multiple analytic gaps — between modes and media, participants and materials, recording and representation. Eliciting the tensions between sensorial closeness and modal distances offers a new space for reflexive research practice and multiple ways of knowing social worlds.
Jokes, rhetoric and embodied racism: a rhetorical discourse analysis of the logics of racist jokes on the internet
Authors: Weaver Simon
Published: June 2011

This article outlines the racist rhetoric employed in anti-black jokes on five internet websites. It is argued that racist jokes can act as important rhetorical devices for serious racisms, and thus work in ways that can support racism in particular readings. By offering a rhetorical discourse analysis of jokes containing embodied racism – or the discursive remains of biological racism – it is shown that internet jokes express two key logics of racism. These logics are inclusion and exclusion. It is argued that inclusion usually inferiorizes and employs race stereotypes whereas exclusion often does not. The article expands this second category by highlighting exclusionary ‘black’ and ‘nigger’ jokes. These categories of non-stereotyped race or ethnic joking have been largely ignored in humour studies because of a reliance on a problematic and celebratory definition of the ethnic joke. Thus a wider definition of racist humour is offered.
Addressing Self-Directed Violence Prevention for Preventive Medicine Practitioners
Authors: Crosby Alex E. , Buckner Ayanna V. , Taylor Beverly D.
Published: June 2011

This article summarizes the field of self-directed violence and its prevention focusing on suicidal behavior. Then it describes ways in which health care practitioners, especially preventive medicine specialists, can play a role in preventing these injuries whether they practice in clinical or community based settings. A review of the importance of suicidal behavior as a public health problem, its epidemiology, and prevention approaches are discussed. Suicidal behavior results from an interaction of risk factors but much is known about these factors and many of the injuries due to this phenomenon are preventable. Prevention of suicidal behavior requires collaboration from many sectors, including health care practitioners. Preventive medicine specialists can address this problem that affects individuals, families, and communities by taking an active part as practitioners, researchers, advocates, and through education.
A Review of Physical and Mental Health Consequences of Child Abuse and Neglect and Implications for Practice
Authors: Leeb Rebecca T. , Lewis Terri , Zolotor Adam J.
Published: June 2011

This article provides an overview of mental and physical health outcomes of child maltreatment to help health care providers identify the consequences of maltreatment and consider treatment options. Child maltreatment is associated with a variety of negative physical and mental health outcomes that affect the individual throughout the lifespan and place a substantial burden on both victims and the population as a whole. The review begins with an overview of the role of physicians in identifying abuse and neglect in the clinic setting. Next, current research findings on physical and mental health outcomes in children, adolescents, and adults are reviewed. Finally, opportunities for primary prevention of abuse and neglect are discussed. Primary prevention strategies can avoid risk for maltreatment, and subsequent interventions for victims have the potential to greatly improve their health.
Specialized cardiological care may be overutilized in urban areas of Québec
Authors: Cohen Alan A , Vanasse Alain , Courteau Josiane ,   (for the PRIMUS research group)
Published: June 2011

Background: Urban/rural differences in secondary cardiovascular disease (CVD) events have previously been observed for Québec. These differences could be attributable to differential utilization of specialized cardiological care, such as revascularization procedures and visits to cardiologists; if this were the case, policies to increase utilization in rural areas would be indicated.

Design: This is a population-based cohort study.

Methods: We analysed mortality and hospital re-admission in Québec within 1 year after an initial cardiovascular event in relation to urban/rural location and specialized care utilization, controlling for demography, comorbidities, and cumulative hospitalization.

Results: Analysis showed higher hospital re-admissions and slightly lower CVD mortality in rural areas, as well as less use of specialized care in rural areas. However, urban/rural differentials were not attributable to differences in utilization of care. Paradoxically, comorbidities were lower among patients who saw specialists.

Conclusions: Ultimately, urban/rural differences in secondary CVD outcomes were not attributable to differences in care utilization or our measures of underlying health status, and were likely due to cultural or lifestyle factors that are both hard to model and hard to change through policy. There appears to be overutilization of specialized care in urban areas, an issue which requires further study. Our results suggest that substantial caution is required when interpreting health service usage data and that critical factors in the relationship between specialized cardiological care and outcomes are still poorly understood at a population level.
Pharmacological treatments for osteoporosis in very elderly people
Authors: Chua Wei Mei , Nandi Novoneel , Masud Tahir
Published: June 2011

Only a few randomized controlled trials investigating antiosteoporotic agents with fracture endpoints have included participants over the age of 80 years. The pivotal trial with alendronic acid had an upper age range of 80 years, although a separate trial that showed a significant reduction in nonvertebral fractures included some participants up to age of 84 years. Risedronate and zoledronic acid are the only bisphosphonates to show a significant reduction in new vertebral, hip and nonvertebral fractures during a 3-year period in those over 80 years of age. In addition, zoledronic acid was associated with a reduction in the rate of new clinical fractures and improved survival in elderly subjects after hip fracture. More recently, denosumab was found to significantly reduce the risk of new radiographic vertebral, hip and nonvertebral fractures in women up to the age of 89 years with osteoporosis. Strontium ranelate and teriparatide have shown fracture reductions in populations that have included subjects over the age of 80 years. There has been evidence to show that a combination of calcium and vitamin D reduces nonvertebral fracture in older populations. The role of vitamin D alone is less clear, although there is the suggestion that it may be effective at higher doses. The burden of osteoporosis is unquestionably rising within our ageing population. More emphasis is therefore required on researching the benefits of these pharmacological agents in very elderly people.
The effect of uncut chip thickness on edge chipping and wheel performance in groove grinding of single crystal silicon
Authors: J Wang J-J , Liao Y-Y , Huang C-Y
Published: June 2011

Achieving a long wheel service life and an acceptable level of edge chipping in the groove grinding of single crystal silicon, such as in the die-sawing process, often requires time-consuming trials for proper setting of important process parameters, including wheel selection, feed, speed, and cutting depth. To better understand the effect of various process parameters on edge chipping and wheel performance, this paper proposes a new process variable, the cutting depth ratio (CDR), to characterize the operating conditions of the groove grinding process. Combining the kinematic features of the grinding process and the material fracture criterion, the CDR, defined as the ratio of the maximum uncut chip thickness to the critical depth of cut of silicon, is employed to investigate the effect of uncut chip thickness on groove edge chipping and wheel performance. The magnitude of edge chipping is shown to steadily increase with increasing CDR, indicating increasing brittle behaviour of the material removal process as the uncut chip thickness increases. By using grinding ratio to correlate with wheel performance, it is shown that the grinding ratio first increases with increasing CDR, and reaches a peak value approximately at a CDR value of 1 before falling off at higher uncut chip thickness. The stochastic nature of the chip thickness is used to explain the finding that the best wheel performance occurs around unity CDR.
Generation of a multipathogen-specific T-cell product for adoptive immunotherapy based on activation-dependent expression of CD154
Authors: Khanna Nina , Stuehler Claudia , Conrad Barbara , Lurati Sarah , Krappmann Sven , Einsele Hermann , Berges Carsten , Topp Max S.
Published: June 2011

Viral and fungal infections remain a leading cause of mortality in patients after hematopoietic stem cell transplantation (HSCT). Adoptive transfer of multipathogen-specific T cells is promising in restoring immunity and thereby preventing and treating infections, but approaches are currently limited because of time-consuming and laborious procedures. Therefore, we investigated a new strategy to simultaneously select T cells specific for viral and fungal pathogens based on activation-dependent expression of CD154. Single- and multipathogen-specific T-cell lines with high specificity for adenovirus (AdV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Candida albicans, and/or Aspergillus fumigatus could be readily generated within 14 days irrespective of the precursor frequency. The T-cell lines responded reproducibly to endogenously processed antigen and specifically proliferated upon antigenic stimulation. Although isolation based on CD154 favors enrichment of CD4+ T cells, AdV-, EBV- and CMV-specific CD8+ T cells could be expanded and demonstrated lysis of target cells. Conversely, T cell–mediated alloreactivity was almost abrogated compared with the starting fraction. This selection and/or expansion strategy may form the basis for future adoptive immunotherapy trials in patients at risk for multiple infections and may be translated to other antigens.
NFATc3 regulates the transcription of genes involved in T-cell activation and angiogenesis
Authors: Urso Katia , Alfranca Arantzazu , Martínez-Martínez Sara , Escolano Amelia , Ortega Inmaculada , Rodríguez Antonio , Redondo Juan Miguel
Published: June 2011

The nuclear factor of activated T cells (NFAT) family of transcription factors plays important roles in many biologic processes, including the development and function of the immune and vascular systems. Cells usually express more than one NFAT member, raising the question of whether NFATs play overlapping roles or if each member has selective functions. Using mRNA knock-down, we show that NFATc3 is specifically required for IL2 and cyclooxygenase-2 (COX2) gene expression in transformed and primary T cells and for T-cell proliferation. We also show that NFATc3 regulates COX2 in endothelial cells, where it is required for COX2, dependent migration and angiogenesis in vivo. These results indicate that individual NFAT members mediate specific functions through the differential regulation of the transcription of target genes. These effects, observed on short-term suppression by mRNA knock-down, are likely to have been masked by compensatory effects in gene-knockout studies.
Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers
Authors: Sáez-Cirión Asier , Hamimi Chiraz , Bergamaschi Anna , David Annie , Versmisse Pierre , Mélard Adeline , Boufassa Faroudy , Barré-Sinoussi Françoise , Lambotte Olivier , Rouzioux Christine , Pancino Gianfranco ,   for the ANRS CO18 Cohort
Published: June 2011

How HIV controllers (HICs) maintain undetectable viremia without therapy is unknown. The strong CD8+ T-cell HIV suppressive capacity found in many, but not all, HICs may contribute to long-lasting viral control. However, other earlier defense mechanisms may be involved. Here, we examined intrinsic HIC cell resistance to HIV-1 infection. After in vitro challenge, monocyte-derived macrophages and anti–CD3-activated CD4+ T cells from HICs showed low HIV-1 susceptibility. CD4 T-cell resistance was independent of HIV-1 coreceptors and affected also SIVmac infection. CD4+ T cells from HICs expressed ex vivo higher levels of p21Waf1/Cip1, which has been involved in the control of HIV-1 replication, than cells from control subjects. However, HIV restriction in anti–CD3-activated CD4+ T cells and macrophages was not associated with p21 expression. Restriction inhibited accumulation of reverse transcripts, leading to reduction of HIV-1 integrated proviruses. The block could be overcome by high viral inocula, suggesting the action of a saturable mechanism. Importantly, cell-associated HIV-1 DNA load was extremely low in HICs and correlated with CD4+ T-cell permissiveness to infection. These results point to a contribution of intrinsic cell resistance to the control of infection and the containment of viral reservoir in HICs.
A honey bee (Apis mellifera L.) PeptideAtlas crossing castes and tissues
Authors: Chan Queenie WT , Parker Robert , Sun Zhi , Deutsch Eric W , Foster Leonard J
Published: June 2011

Background

Honey bees are a mainstay of agriculture, contributing billions of dollars through their pollination activities. Bees have been a model system for sociality and group behavior for decades but only recently have molecular techniques been brought to study this fascinating and valuable organism. With the release of the first draft of its genome in 2006, proteomics of bees became feasible and over the past five years we have amassed in excess of 5E+6 MS/MS spectra. The lack of a consolidated platform to organize this massive resource hampers our ability, and that of others, to mine the information to its maximum potential.

Results

Here we introduce the Honey Bee PeptideAtlas, a web-based resource for visualizing mass spectrometry data across experiments, providing protein descriptions and Gene Ontology annotations where possible. We anticipate that this will be helpful in planning proteomics experiments, especially in the selection of transitions for selected reaction monitoring. Through a proteogenomics effort, we have used MS/MS data to anchor the annotation of previously undescribed genes and to re-annotate previous gene models in order to improve the current genome annotation.

Conclusions

The Honey Bee PeptideAtlas will contribute to the efficiency of bee proteomics and accelerate our understanding of this species. This publicly accessible and interactive database is an important framework for the current and future analysis of mass spectrometry data.
Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity
Authors: Sahl Jason W , Johnson J Kristie , Harris Anthony D , Phillippy Adam M , Hsiao William W , Thom Kerri A , Rasko David A
Published: June 2011

Background

Acinetobacter baumannii has recently emerged as a significant global pathogen, with a surprisingly rapid acquisition of antibiotic resistance and spread within hospitals and health care institutions. This study examines the genomic content of three A. baumannii strains isolated from distinct body sites. Isolates from blood, peri-anal, and wound sources were examined in an attempt to identify genetic features that could be correlated to each isolation source.

Results

Pulsed-field gel electrophoresis, multi-locus sequence typing and antibiotic resistance profiles demonstrated genotypic and phenotypic variation. Each isolate was sequenced to high-quality draft status, which allowed for comparative genomic analyses with existing A. baumannii genomes. A high resolution, whole genome alignment method detailed the phylogenetic relationships of sequenced A. baumannii and found no correlation between phylogeny and body site of isolation. This method identified genomic regions unique to both those isolates found on the surface of the skin or in wounds, termed colonization isolates, and those identified from body fluids, termed invasive isolates; these regions may play a role in the pathogenesis and spread of this important pathogen. A PCR-based screen of 74 A. baumanii isolates demonstrated that these unique genes are not exclusive to either phenotype or isolation source; however, a conserved genomic region exclusive to all sequenced A. baumannii was identified and verified.

Conclusions

The results of the comparative genome analysis and PCR assay show that A. baumannii is a diverse and genomically variable pathogen that appears to have the potential to cause a range of human disease regardless of the isolation source.
Transcriptomics and molecular evolutionary rate analysis of the bladderwort (Utricularia), a carnivorous plant with a minimal genome
Authors: Ibarra-Laclette Enrique , Albert Victor A , Pérez-Torres Claudia A , Zamudio-Hernández Flor , Ortega-Estrada María de J , Herrera-Estrella Alfredo , Herrera-Estrella Luis
Published: June 2011

Background

The carnivorous plant Utricularia gibba (bladderwort) is remarkable in having a minute genome, which at ca. 80 megabases is approximately half that of Arabidopsis. Bladderworts show an incredible diversity of forms surrounding a defined theme: tiny, bladder-like suction traps on terrestrial, epiphytic, or aquatic plants with a diversity of unusual vegetative forms. Utricularia plants, which are rootless, are also anomalous in physiological features (respiration and carbon distribution), and highly enhanced molecular evolutionary rates in chloroplast, mitochondrial and nuclear ribosomal sequences. Despite great interest in the genus, no genomic resources exist for Utricularia, and the substitution rate increase has received limited study.

Results

Here we describe the sequencing and analysis of the Utricularia gibba transcriptome. Three different organs were surveyed, the traps, the vegetative shoot bodies, and the inflorescence stems. We also examined the bladderwort transcriptome under diverse stress conditions. We detail aspects of functional classification, tissue similarity, nitrogen and phosphorus metabolism, respiration, DNA repair, and detoxification of reactive oxygen species (ROS). Long contigs of plastid and mitochondrial genomes, as well as sequences for 100 individual nuclear genes, were compared with those of other plants to better establish information on molecular evolutionary rates.

Conclusion

The Utricularia transcriptome provides a detailed genomic window into processes occurring in a carnivorous plant. It contains a deep representation of the complex metabolic pathways that characterize a putative minimal plant genome, permitting its use as a source of genomic information to explore the structural, functional, and evolutionary diversity of the genus. Vegetative shoots and traps are the most similar organs by functional classification of their transcriptome, the traps expressing hydrolytic enzymes for prey digestion that were previously thought to be encoded by bacteria. Supporting physiological data, global gene expression analysis shows that traps significantly over-express genes involved in respiration and that phosphate uptake might occur mainly in traps, whereas nitrogen uptake could in part take place in vegetative parts. Expression of DNA repair and ROS detoxification enzymes may be indicative of a response to increased respiration. Finally, evidence from the bladderwort transcriptome, direct measurement of ROS in situ, and cross-species comparisons of organellar genomes and multiple nuclear genes supports the hypothesis that increased nucleotide substitution rates throughout the plant may be due to the mutagenic action of amplified ROS production.
Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity
Authors: Qi Wentao , Weber Christopher R , Wasland Kaarin , Savkovic Suzana D
Published: June 2011

Background

Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity.

Methods

The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53.

Results

Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest.

Conclusion

These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer.
The role of female hormones on lung function in chronic lung diseases
Authors: Tam Anthony , Morrish Don , Wadsworth Samuel , Dorscheid Delbert , Man SF Paul , Sin Don D
Published: June 2011

Background

The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle in female patients with airways disease but not in women without disease, suggesting that circulating estradiol and progesterone may be involved in this process.

Discussion

In asthma, estradiol shuttles adaptive immunity towards the TH2 phenotype while in smokers estrogens may be involved in the generation of toxic intermediate metabolites in the airways of female smokers, which may be relevant in COPD pathogenesis. In CF, estradiol has been demonstrated to up-regulate MUC5B gene in human airway epithelial cells and inhibit chloride secretion in the airways. Progesterone may augment airway inflammation.

Taken together, clinical and in-vivo data have demonstrated a sex-related difference in that females may be more susceptible to the pathogenesis of lung diseases. In this paper, we review the effect of female sex hormones in the context of these inflammatory airway diseases.
2-hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase
Authors: Dan Phyllis , Edvardson Simon , Bielawski Jacek , Hama Hiroko , Saada Ann
Published: June 2011

Fatty acid 2-hydroxylase (FA2H) is the enzyme responsible for the hydroxylation of free fatty acids prior to their incorporation into 2-hydroxylated sphingolipids, which are the major constituents of the myelin leaflet. Mutated FA2H has been associated with neurodegenerative diseases. Decreased FA2H activity was demonstrated only in vitro, but not in patient tissues. In this study we characterized the 2-hydroxylated sphingomyelin (SM) profiles in blood and fibroblasts from patients harboring a deleterious FA2H mutatation, and found that hydroxylated fatty acid sphingomyelin is present in normal amounts in patient lymphocytes, but decreased to a different extent in fibroblasts and erythrocytes.
HAPIscreen, a method for high-throughput aptamer identification
Authors: Dausse Eric , Taouji Saïd , Evadé Laetitia , Di Primo Carmelo , Chevet Eric , Toulmé Jean-Jacques
Published: June 2011

Background

Aptamers are oligonucleotides displaying specific binding properties for a predetermined target. They are selected from libraries of randomly synthesized candidates through an in vitro selection process termed SELEX (Systematic Evolution of Ligands by EXponential enrichment) alternating selection and amplification steps. SELEX is followed by cloning and sequencing of the enriched pool of oligonucleotides to enable comparison of the selected sequences. The most represented candidates are then synthesized and their binding properties are individually evaluated thus leading to the identification of aptamers. These post-selection steps are time consuming and introduce a bias to the expense of poorly amplified binders that might be of high affinity and are consequently underrepresented. A method that would circumvent these limitations would be highly valuable.

Results

We describe a novel homogeneous solution-based method for screening large populations of oligonucleotide candidates generated from SELEX. This approach, based on the AlphaScreen® technology, is carried out on the exclusive basis of the binding properties of the selected candidates without the needs of performing a priori sequencing. It therefore enables the functional identification of high affinity aptamers. We validated the HAPIscreen (High throughput APtamer Identification screen) methodology using aptamers targeted to RNA hairpins, previously identified in our laboratory. We then screened pools of candidates issued from SELEX rounds in a 384 well microplate format and identify new RNA aptamers to pre-microRNAs.

Conclusions

HAPIscreen, an Alphascreen®-based methodology for the identification of aptamers is faster and less biased than current procedures based on sequence comparison of selected oligonucleotides and sampling binding properties of few individuals. Moreover this methodology allows for screening larger number of candidates. Used here for selecting anti-premiR aptamers, HAPIscreen can be adapted to any type of tagged target and is fully amenable to automation.
Growth, physicochemical properties, and morphogenesis of Chinese wild-type PRV Fa and its gene-deleted mutant strain PRV SA215
Authors: Zhu Ling , Yi Yue , Xu Zhiwen , Cheng Lu , Tang Shanhu , Guo Wanzhu
Published: June 2011

Background

PRV Fa is common in China and causes most of the pseudorabies in the pig industry. A PRV SA215 strain with deleted gE, gI, and TK genes was constructed to develop a commercial attenuated live vaccine. However, the physicochemical properties, growth pattern, penetration kinetics, and morphogenesis of the PRV SA215 and its parental PRV Fa strain are unclear.

Results

A series of experiments were conducted to characterize both strains and provide more information. PRV Fa and PRV SA215 were found to have similar penetration patterns, with about 5 min half-time of penetration. The SA215 strain exhibited a slight delay in entry compared with PRV Fa. In the one-step growth test, the titers of the SA215 strain were first detected at 8 h, rapidly increased, and peaked at 12 h. A plateau was formed between 12-36 h of culturing. PRV SA215 showed delayed replication and approximately 10-30-fold lower titers during 0-16 h of culturing compared with the PRV-Fa strain. After 16 h, the PRV Fa titers dramatically decreased, whereas those of PRV SA215 were prolonged to 36 h and reached a titer value equal to that of PRV Fa and then decreased. Both strains were sensitive to both heat and acid-alkali treatments; however, PRV Fa was relatively more stable to heat treatment than PRV SA215. Both strains could propagate in the cultures with pH values from 5.0 to 9.0. Cultures with pH below 3.0 or above 11.0 were fatal to both strains. Both strains had considerable resistance to freeze-thawing treatments. Morphogenetic investigations showed that typical phases in the maturation pathway were observed in the PRV Fa-infected PK15 cells, whereas secondary envelopment was not observed in the PRV SA215 strain. Instead, capsid aggregations with concomitants of electrodense materials were observed.

Conclusions

These results suggest that PRV SA215 is a promising strain for vaccine development
A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice
Authors: Lin Wenyao , Fan Huiying , Cheng Xiaoliang , Ye Yu , Chen Xiaowei , Ren Tao , Qi Wenbao , Liao Ming
Published: June 2011

Background

Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them.

Results

The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice.

Conclusion

BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.
Involvement of the Cav3.2 T-Type Calcium Channel in Thalamic Neuron Discharge Patterns
Authors: Liao Yi-Fang , Tsai Meng-Li , Chen Chien-Chang , Yen Chen-Tung
Published: June 2011

Background:

Mice that have defects in their low-threshold T-type calcium channel (T-channel) genes show altered pain behaviors. The changes in the ratio of nociceptive neurons and the burst firing property of reticular thalamic (RT) and ventroposterior (VP) neurons in Cav3.2 knockout (KO) mice were studied to test the involvement of thalamic T-channel and burst firing activity in pain function.

Results:

Under pentobarbital or urethane anesthesia, the patterns of tonic and burst firings were recorded in functionally characterized RT and VPL neurons of Cav3.2 KO mice. Many RT neurons were nociceptive (64% under pentobarbital anesthesia and 50% under urethane anesthesia). Compared to their wild-type (WT) controls, fewer nociceptive RT neurons were found in Cav3.2 KO mice. Both nociceptive and tactile RT neurons showed fewer bursts in Cav3.2 KO mice. Within a burst, RT neurons of Cav3.2 KO mice had a lower spike frequency and less-prominent accelerando-decelerando change. In contrast, VP neurons of Cav3.2 KO mice showed a higher ratio of bursts and a higher discharge rate within a burst than those of the WT control. In addition, the long-lasting tonic firing episodes in RT neurons of the Cav3.2 KO had less stereotypic regularity than their counterparts in WT mice.

Conclusions:

RT might be important in nociception of the mouse. In addition, we showed an important role of Cav3.2 subtype of T-channel in RT burst firing pattern. The decreased occurrence and slowing of the bursts in RT neurons might cause the increased VP bursts. These changes would be factors contributing to alternation of pain behavior in the Cav3.2 KO mice.
A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial
Authors: Zhang Chi , Jiang Miao , Lu Aiping
Published: June 2011

Background

The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns.

Methods/Design

This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria.

Discussion

The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses.

Trial registration

ChiCTR-TRC-10000989
Association of promoter methylation with histologic type and pleural indentation in non-small cell lung cancer (NSCLC)
Authors: Ji Meiju , Zhang Yong , Shi Bingyin , Hou Peng
Published: June 2011

Background

Lung cancer is a major cause of death worldwide. Gene promoter methylation is a major inactivation mechanism of tumor-related genes, some of which can be served as a biomarker for early diagnosis and prognosis evaluation of lung cancer.

Methods

We determined the promoter methylation of 6 genes using quantitative methylation-specific PCR (Q-MSP) technique in 96 clinically well-characterized non-small cell lung cancer (NSCLC).

Results

Highly frequent promoter methylation was found in NSCLC. With 100% diagnostic specificity, high sensitivity, ranging from 44.9 to 84.1%, was found for each of the 6 genes. Our data also showed that promoter methylation was closely associated with histologic type. Most of genes were more frequently methylated in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Moreover, promoter methylation significantly increased the risk of pleural indentation in NSCLC.

Conclusion

Our findings provided evidences that multiple genes were aberrantly methylated in lung tumorigenesis, and demonstrated the promoter methylation was closely associated with clinicopathologic characteristics of NSCLC. More importantly, we first revealed promoter methylation may be served as a potentially increased risk factor for pleural indentation of NSCLC patients.
Report from the Second International Symposium on Animal Genomics for Animal Health: Critical Needs, Challenges and Potential Solutions
Authors: Bishop Steve C , Lunney Joan K , Pinard-van der Laan Marie-Hélène , Gay Cyril G
Published: June 2011

The second International Symposium on Animal Genomics for Animal Health held in Paris, France 31 May-2 June, 2010, assembled more than 140 participants representing research organizations from 40 countries. The symposium included a roundtable discussion on critical needs, challenges and opportunities, and a forward look at the potential applications of animal genomics in animal health research. The aim of the roundtable discussion was to foster a dialogue between scientists working at the cutting edge of animal genomics research and animal health scientists. Importantly, stakeholders were included to provide input on priorities and the potential value of animal genomics to the animal health community. In an effort to facilitate the roundtable discussion, the organizers identified four priority areas to advance the use of genome-enabled technologies in animal health research. Contributions were obtained through open discussions and a questionnaire distributed at the start of the symposium. This report provides the outcome of the roundtable discussion for each of the four priority areas. For each priority, problems are identified, including potential solutions and recommendations. This report captures key points made by symposium participants during the roundtable discussion and serves as a roadmap to steer future research priorities in animal genomics research.