bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Capability Scale
Authors: Resnick Barbara , Boltz Marie , Galik Elizabeth , Wells Chris
Published: June 2012

The purpose of this study was to describe the psychometric testing of the Basic Physical Capability Scale. The study was a secondary data analysis of combined data sets from three studies. Study participants included 93 older adults, recruited from 2 acute-care settings and 110 older adults living in long-term care facilities. Rasch analysis was used for the testing of the measurement model. There was some support for construct validity based on the fit of the items to the scale across both samples. In addition, there was support for hypothesis testing as physical function was significantly associated with physical capability. There was evidence for internal consistency (Alpha coefficients of .77-.83) and interrater reliability based on an intraclass correlation of .81. This study provided preliminary support for the reliability and validity of the Basic Physical Capability Scale, and guidance for scale revisions and continued use.
The Optimal Structure of Commodity Taxation in a Monopoly with Tax Avoidance or Evasion
Authors: Goerke Laszlo
Published: June 2012

If tax obligations are met, the balanced-budget substitution of an ad valorem tax on output for a specific tax not only raises a monopolist’s production but also represents a Pareto improvement. However, if tax avoidance or evasion is feasible and the marginal costs of such actions decline with the legal tax burden, a monopolist will respond to a balanced-budget substitution of an ad valorem tax for a specific tax by reducing output, while profits remain constant. Therefore, in the presence of tax avoidance or evasion activities, a move toward specific taxation can represent a Pareto improvement.
Dispute settlement in world politics: States, supranational prosecutors, and compliance
Authors: Tallberg Jonas , McCall Smith James
Published: June 2012

This article addresses one prominent expression of the interplay between politics and law in international cooperation: the dynamics of bargaining in the settling of compliance disputes. Our central argument is that the formal structure of dispute settlement systematically shapes the likelihood and terms of negotiated compliance settlements. We introduce an ideal type distinction between interstate dispute settlement, where the authority to sue states for non-compliance resides exclusively with states, and supranational dispute settlement, where this authority is partly or entirely delegated to a commission or secretariat with a prosecutorial function. We hypothesize that systems relying on supranational prosecution are more effective in addressing non-compliance, and more likely to mediate the impact of power asymmetries on dispute settlement outcomes, compared to systems relying on state-initiated complaints only. We find support for this proposition in an in-depth comparison of dispute settlement and compliance bargaining in the World Trade Organization and the European Union, and in a brief survey of experiences from other international organizations.
White matter and development in children with an autism spectrum disorder
Authors: Mak-Fan Kathleen M , Morris Drew , Vidal Julie , Anagnostou Evdokia , Roberts Wendy , Taylor Margot J
Published: June 2012

Recent research suggests that brain development follows an abnormal trajectory in children with autism spectrum disorders (ASD). The current study examined changes in diffusivity with age within defined white matter tracts in a group of typically developing children and a group of children with an ASD, aged 6 to 14 years. Age by group interactions were observed for frontal, long distant, interhemispheric and posterior tracts, for longitudinal, radial and mean diffusivity, but not for fractional anisotropy. In all cases, these measures of diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. This supports the hypothesis of an abnormal developmental trajectory of white matter in this population, which could have profound effects on the development of neural connectivity and contribute to atypical cognitive development in children with ASD.
Budgetjam! A communications intervention in the political-economic crisis in Ireland
Authors: Titley Gavan
Published: June 2012

This essay reflects on a communications intervention organized immediately following the ‘bailout’ provided to Ireland by the troika of the European Commission, the International Monetary Fund (IMF) and the European Central Bank (ECB), and preceding the implementation of an ‘austerity’ budget designed to further the transfer of banking debt to the sovereign. Reacting to the steadfast official narrative that ‘there is no alternative’, and the general failure of mainstream journalism to question the framing of the ‘bailout’, a network of political and community activists, journalists and academics experimented with ways of challenging the dominant framing of the crisis.
The strategic ritual of emotionality: A case study of Pulitzer Prize-winning articles
Authors: Wahl-Jorgensen Karin
Published: June 2012

Taking as its vantage point Gaye Tuchman’s (1972) notion of the strategic ritual of objectivity, this article argues that there is also a strategic ritual of emotionality in journalism – an institutionalized and systematic practice of journalists infusing their reporting with emotion. To examine the strategic ritual of emotionality, the article considers Pulitzer Prize-winning articles between 1995 and 2011, taking the prize as a marker of cultural capital in the journalistic field. A coding scheme for a basic content analysis was developed on the basis of scholarly insights into journalistic narratives, as well as discourse analytic approaches associated with appraisal theory. The analysis indicates that the analyzed stories rely heavily on emotional story-telling. The strategic ritual of emotionality manifests itself in the overwhelming use of anecdotal leads, personalized story-telling and expressions of affect. Journalists ‘outsource’ emotional labor by describing the emotions of others, and drawing on sources to discuss their emotions.
Seeking the analytic imagination: reflections on the process of interpreting qualitative data
Authors: James Allison
Published: June 2012

In the light of the changing landscape of social research, this article explores the role of the analytic imagination in the process of qualitative data analysis. It argues that while team research, secondary data analysis and the use of computerized qualitative data analysis packages may be altering the ways in which research and analysis are carried out, this need not change the processes of interpretation that are at the heart of qualitative data analysis. Here, as the article explores, imaginative acts are key to the analytical craftsmanship involved in interpretive analysis. This a process illustrated through the analysis of parent and child narratives gathered during a project about families and food.
British Muslims, British soldiers: Cultural citizenship in the new imperialism
Authors: Qureshi Kaveri , Zeitlyn Benjamin
Published: June 2012

The discursive positioning of Muslims as a ‘security threat’ or ‘enemy within’, in government policies and the media, has cast young Muslim men in particular as criminalized anti-citizens. Meanwhile, since the inception of the Afghanistan campaign, the soldier has become increasingly prominent as a figure of militarized citizenship in the public sphere. This article juxtaposes accounts from Pakistani Muslim youth in the West Midlands with those of soldiers and family members involved with the Hero Net online community, attending to the notion of cultural citizenship – namely, the everyday subjective experience of national belonging beyond its legal–political aspects. Our research suggests that, for both groups, mindful critique or dissent are central to the process through which individuals are brought into being in relation to the nation-state. However, we demonstrate that formations of cultural citizenship in Britain continue to be informed by the logics of race and orientalism. The article offers insights into how gendered and racialized formations of citizenship conjoin with imperialism and militarization.
The inegalitarian ethos
Authors: McTernan Emily
Published: June 2012

In Cohen’s vision of the just society, there would be no need for unequalizing incentives so as to benefit the least well-off; instead, people would be motivated by an egalitarian ethos to work hard and in the most socially productive jobs. As such, Cohen appears to offer a way to mitigate the trade-off of equality for efficiency that often characterizes theorizing about distributive justice. This article presents an egalitarian challenge to Cohen’s vision of the just society. I argue that a society where all internalized the egalitarian ethos would be one lacking equal respect among its members, in which certain groups lacked the grounds of self-respect. Section 1 defends equal respect and a form of equality of self-respect as values with broad-based appeal to egalitarians, and argues that a particular form of hierarchy would undermine both equal respect and the grounds of self-respect. Sections 2 and 3 reveal that just such a hierarchy would emerge in a society in which all had internalized the egalitarian ethos, in the case of both carers and the untalented. Thus, Cohen’s proposed society is shown to fail to unite equality and efficiency. Instead, Cohen’s society would be characterized by a lack of equality.
World poverty, positive duties, and the overdemandingness objection
Authors: Sonderholm Jorn
Published: June 2012

One objection that has been consistently raised for theorists who are committed to the idea that we have a positive duty to aid the global poor is the overdemandingness objection. This article is a critical discussion of this objection. First, the objection is laid out in some detail. A number of influential attempts to meet the overdemandingness objection are then discussed, and it is argued that they all fail in their intended purpose. The conclusion of the article is not that the overdemandingness objection cannot be met. Rather, the conclusion is that the overdemandingness objection constitutes a serious challenge to anyone who accepts the objection and goes beyond the standard libertarian doctrine and commits herself to the existence of positive duties to aid the global poor.
From effective partnerships to sulking in the corner: the public health response to multinationals
Authors: Bisits Bullen Piroska A.
Published: June 2012

Multinationals and the for-profit sector evoke a range of responses from public health professionals - from enthusiasm through to distain and anger. Several sessions at the conferences of the International Union for Health Promotion and Education (IUHPE) and of the American Public Health Association (APHA) in 2010 addressed issues related to multinationals, trade and public-private partnerships. However, there was no representation from the for-profit sector at any of these events. This commentary argues that, regardless of whether public health professionals agree or disagree with the actions of multinationals, maintaining a dialogue with them is essential. Recommendations are given for engaging effectively with the for-profit sector.
Inclusive Education for Learners With Disabilities in Botswana Primary Schools
Authors: Mukhopadhyay Sourav , Nenty H. Johnson , Abosi Okechukwu
Published: June 2012

Based on the findings of a qualitative case study, this article describes the experiences of key stakeholders about the inclusion of learners with disabilities in regular schools in the South Central Region of Botswana. Multiple stakeholders, such as school-heads, general education teachers, learners with disabilities, and their peers, from six elementary schools participated in this research. The data collection methods included focus group discussions, school and classroom observations, and document analysis. Findings indicate that most of the teachers preferred to include learners with mild disabling conditions compared with learners with severe to profound disabling conditions. School-heads raised concerns such as inadequate training in special education, lack of resources, and high student–teacher ratio as barriers to successful implementation of inclusive education. In contrast to this, the students’ peers expressed high levels of acceptance of learners with disabilities. This reflects Botswana’s history of diversity and culture incorporating regional ethnic differences. It is a real strength to build on in the movement toward fully inclusive education.
DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells
Authors: Hosszu Kinga K. , Valentino Alisa , Vinayagasundaram Uma , Vinayagasundaram Rama , Joyce M. Gordon , Ji Yan , Peerschke Ellinor I. B. , Ghebrehiwet Berhane
Published: June 2012

C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the 2 C1q receptors found on the DC surface—gC1qR and cC1qR—lack a direct conduit into intracellular elements, we postulated that the receptors must form complexes with transmembrane partners. In the present study, we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry, and immunoprecipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and both intact C1q and the globular portion of C1q bound to DC-SIGN. Whereas IgG reduced this binding significantly, the Arg residues (162-163) of the C1q-A chain, which are thought to contribute to the C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was reduced significantly in the absence of Ca2+ and by preincubation of DC-SIGN with mannan, suggesting that C1q binds to DC-SIGN at its principal Ca2+-binding pocket, which has increased affinity for mannose residues. Antigen-capture ELISA and immunofluorescence microscopy revealed that C1q and gC1qR associate with DC-SIGN on blood DC precursors and immature DCs. The results of the present study suggest that C1q/gC1qR may regulate DC differentiation and function through the DC-SIGN–mediated induction of cell-signaling pathways.
Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques
Authors: Sköld Annette E. , Hasan Maroof , Vargas Leonardo , Saidi Hela , Bosquet Nathalie , Le Grand Roger , Smith C. I. Edvard , Spetz Anna-Lena
Published: June 2012

TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human monocyte-derived dendritic cells up-regulate maturation markers and secrete proinflammatory cytokines on treatment with the synthetic TLR3 ligand polyinosine-polycytidylic acid (poly I:C). These events were inhibited in cultures with ssDNA-ODNs. Poly I:C activation of nonhematopoietic cells was also inhibited by ssDNA-ODNs. The uptake of poly I:C into cells was reduced in the presence of ssDNA-ODNs, preventing TLR3 engagement from occurring. To confirm this inhibition in vivo, we administered ssDNA-ODNs and poly I:C, alone or in combination, via the intranasal route in cynomolgus macaques. Proinflammatory cytokines were detected in nasal secretions in the poly I:C group, while the levels were reduced in the groups receiving ssDNA-ODNs or both substances. Our results demonstrate that TLR3-triggered immune activation can be modulated by ssDNA-ODNs and provide evidence of dampening proinflammatory cytokine release in the airways of cynomolgus macaques. These findings may open novel perspectives for clinical strategies to prevent or treat inflammatory conditions exacerbated by TLR3 signaling.
Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands
Authors: Yang Won Ho , Nussbaum Claudia , Grewal Prabhjit K. , Marth Jamey D. , Sperandio Markus
Published: June 2012

Binding of selectins to their glycan ligands is a prerequisite for successful leukocyte trafficking. During synthesis and transport through the secretory pathway, selectin ligands are constructed with the participation of one or more sialyltransferases of the ST3Gal subfamily. Previous studies established that ST3Gal-IV only partially contributes to selectin ligand formation, indicating that other ST3Gal-sialyltransferases are involved. By generating and analyzing St3gal6-null mice and St3gal4/St3gal6 double-deficient mice, in the present study, we found that binding of E- and P-selectin to neutrophils and L-selectin binding to lymph node high endothelial venules is reduced in the absence of ST3Gal-VI and to a greater extent in double-deficient mice. In an ex vivo flow chamber assay, P- and E-selectin–dependent leukocyte rolling was mildly reduced in St3gal6-null mice and more severely in double-deficient mice. In inflamed cremaster muscle venules of St3gal6-null mice, we found impaired P-selectin–dependent, but not E-selectin–dependent leukocyte rolling, whereas in double-deficient mice, E-selectin–dependent rolling was almost completely absent. Furthermore, neutrophil recruitment into the inflamed peritoneal cavity and lymphocyte homing to secondary lymphoid organs were impaired in St3gal6-null mice and more severely in double-deficient mice. The results of the present study demonstrate the coordinated participation of both ST3Gal-VI and ST3Gal-IV in the synthesis of functional selectin ligands.
Fatigue in COPD: association with functional status and hospitalisations
Authors: Paddison Johanna Susan , Effing Tanya W. , Quinn Stephen , Frith Peter A.
Published: June 2012

This study aimed to examine the importance of fatigue as a clinical indicator in chronic obstructive pulmonary disease (COPD), by analysing its relationship with COPD severity and ability to predict risk of hospitalisation, and by comparing the intensity of fatigue in stable COPD patients with levels of fatigue reported by patients with other chronic conditions.

We studied 100 consecutive patients attending assessment clinics before pulmonary rehabilitation. Both questionnaire and physiological data were collected. Partial correlations, multiple linear regressions and Cox proportional hazard models/negative binomial regressions were used to address the research questions.

A significant relationship existed between fatigue and COPD severity. Fatigue reports predicted future hospitalisation risk. Compared to the lowest third of patients, the third of patients reporting the most intense fatigue showed a 10-fold increase in risk of hospitalisation (fatigue experiences hazard ratio (HR) 10.2, 95% CI 2.66–38.86; fatigue impacts HR 10.7, 95% CI 2.76–41.65). Our COPD sample reported fatigue scores of similar intensity to colorectal cancer patients and HIV-positive patients.

While fatigue is significantly related to COPD functional severity, fatigue data also capture independent information. Fatigue reports can contribute to predictions of hospitalisation risk.
Cost-effectiveness of tiotropiumversussalmeterol: the POET-COPD trial
Authors: Hoogendoorn Martine , Al Maiwenn J. , Beeh Kai-Michael , Bowles David , Graf von der Schulenburg J. Matthias , Lungershausen Juliane , Monz Brigitta U. , Schmidt Hendrik , Vogelmeier Claus , Rutten-van Mölken Maureen P.M.H.
Published: June 2012

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropiumversussalmeterol followed by a 5-yr model-based CEA.

The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs).

1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55–195) and €170 (95% UI €77–260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010–0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19–157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective.

Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.
Hearing loss in patients on treatment for drug-resistant tuberculosis
Authors: Seddon James A. , Godfrey-Faussett Peter , Jacobs Kayleen , Ebrahim Adam , Hesseling Anneke C. , Schaaf H. Simon
Published: June 2012

The treatment of drug-resistant (DR)-tuberculosis (TB) necessitates the use of second-line injectable anti-TB drugs which are associated with hearing loss. Hearing loss affects communication and the development of language and social skills in children. This review describes the pathophysiology of hearing loss and the testing methodologies that can be employed. It is the first paper to systematically review the literature regarding hearing loss in those treated for DR-TB. In the studies identified, the methodology used to test for and to classify hearing loss is inconsistent and children and those with HIV are poorly represented. This review describes existing guidelines and suggests management strategies when hearing loss is found. It describes the challenges of testing hearing in the developing world contexts where the majority of patients with DR-TB are treated. Finally it makes the recommendation that a standardised testing methodology and classification system should be used.
Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency
Authors: Stone Helen , McNab Gillian , Wood Alice M. , Stockley Robert A. , Sapey Elizabeth
Published: June 2012

There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with α1-antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups.

Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B4(LTB4) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state.

There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB4compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability.

There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.
Atypical patterns in portable monitoring for sleep apnoea: features of nocturnal epilepsy?
Authors: Parrino Liborio , Milioli Giulia , Grassi Andrea , De Paolis Fernando , Riccardi Silvia , Colizzi Elena , Bosi Marcello , Terzano Mario Giovanni
Published: June 2012

Atypical cardiorespiratory patterns can be found during routine clinical use of portable monitoring for diagnosis of sleep-disordered breathing (SDB).

Over 1,000 consecutive portable recordings were analysed to study the potential ictal nature of stereotyped cardiorespiratory and motor patterns. Snoring, airflow, thoracic effort, pulse rate, body position, oxygen saturation and activity of the anterior tibialis muscles were quantified. Recordings showing stereotyped polygraphic patterns recurring throughout the night, but without the features of sleep apnoea (apnoea/hypopnoea index <5 events·h−1), were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography.

A total of 15 recordings showing repeated polygraphic patterns characterised by a sequence of microphone activation, respiratory activity atypical for sleep and wakefulness, heart rate acceleration and limb movements, followed by body position change, were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography that showed frontal epileptic discharges triggering periodic electroencephalographic arousals, autonomic activation and stereotyped motor patterns. A diagnosis of nocturnal frontal lobe epilepsy (NFLE) was established for all patients.

NFLE should be taken into consideration in patients with stereotyped and recurrent behavioural features during portable monitoring carried out for diagnosis of SDB.
Unrecognised obstructive sleep apnoea is common in severe peripheral arterial disease
Authors: Utriainen Karri T. , Airaksinen Juhani K. , Polo Olli , Raitakari Olli T. , Pietilä Mikko J. , Scheinin Harry , Helenius Hans Y. , Leino Kari A. , Kentala Erkki S. , Jalonen Jouko R. , Hakovirta Harri , Salo Tiina M. , Laitio Timo T.
Published: June 2012

Patients needing surgery for peripheral arterial disease (PAD) represent a severe form of atherosclerosis with an overall 5-yr mortality of 30% after revascularisation. The aetiology for poor post-operative clinical outcome in these high-risk patients is not fully established. Obstructive sleep apnoea (OSA) is associated with atherosclerosis and is an independent risk factor for fatal and nonfatal cardiac events. Here, we determine the prevalence of undiagnosed OSA in a homogenous group of PAD patients undergoing subinguinal surgical revascularisation.

82 consecutive patients (mean age 67±9 yrs, 52 males) with sinus rhythm and without congestive heart failure or previously diagnosed OSA were enrolled for pre-operative polysomnography and echocardiography.

OSA was present in 70 (85%) patients (95% CI 75–93%), of whom 24 (34%) had severe OSA. OSA was mostly asymptomatic, and age- and sex-adjusted multivariate regression analysis showed no relation to obesity, metabolic syndrome or any manifestation of atherosclerosis, other than PAD. Left ventricular ejection fraction (p = 0.002) and high-density lipoprotein/total cholesterol ratio (p = 0.03) were the only independent predictors for the severity of OSA.

Thus, prevalence of OSA is unexpectedly high in patients with PAD and is not related to classical risk factors of sleep apnoea.
BioWord: A sequence manipulation suite for Microsoft Word
Authors: Anzaldi Laura J , Muñoz-Fernández Daniel , Erill Ivan
Published: June 2012

Background

The ability to manipulate, edit and process DNA and protein sequences has rapidly become a necessary skill for practicing biologists across a wide swath of disciplines. In spite of this, most everyday sequence manipulation tools are distributed across several programs and web servers, sometimes requiring installation and typically involving frequent switching between applications. To address this problem, here we have developed BioWord, a macro-enabled self-installing template for Microsoft Word documents that integrates an extensive suite of DNA and protein sequence manipulation tools.

Results

BioWord is distributed as a single macro-enabled template that self-installs with a single click. After installation, BioWord will open as a tab in the Office ribbon. Biologists can then easily manipulate DNA and protein sequences using a familiar interface and minimize the need to switch between applications. Beyond simple sequence manipulation, BioWord integrates functionality ranging from dyad search and consensus logos to motif discovery and pair-wise alignment. Written in Visual Basic for Applications (VBA) as an open source, object-oriented project, BioWord allows users with varying programming experience to expand and customize the program to better meet their own needs.

Conclusions

BioWord integrates a powerful set of tools for biological sequence manipulation within a handy, user-friendly tab in a widely used word processing software package. The use of a simple scripting language and an object-oriented scheme facilitates customization by users and provides a very accessible educational platform for introducing students to basic bioinformatics algorithms.
The language of gene ontology: a Zipf’s law analysis
Authors: Kalankesh Leila Ranandeh , Stevens Robert , Brass Andy
Published: June 2012

Background

Most major genome projects and sequence databases provide a GO annotation of their data, either automatically or through human annotators, creating a large corpus of data written in the language of GO. Texts written in natural language show a statistical power law behaviour, Zipf’s law, the exponent of which can provide useful information on the nature of the language being used. We have therefore explored the hypothesis that collections of GO annotations will show similar statistical behaviours to natural language.

Results

Annotations from the Gene Ontology Annotation project were found to follow Zipf’s law. Surprisingly, the measured power law exponents were consistently different between annotation captured using the three GO sub-ontologies in the corpora (function, process and component). On filtering the corpora using GO evidence codes we found that the value of the measured power law exponent responded in a predictable way as a function of the evidence codes used to support the annotation.

Conclusions

Techniques from computational linguistics can provide new insights into the annotation process. GO annotations show similar statistical behaviours to those seen in natural language with measured exponents that provide a signal which correlates with the nature of the evidence codes used to support the annotations, suggesting that the measured exponent might provide a signal regarding the information content of the annotation.
Significance of decoy receptor 3 (Dcr3) and external-signal regulated kinase 1/2 (Erk1/2) in gastric cancer
Authors: Yang Donghai , Fan Xin , Yin Ping , Wen Qiang , Yan Feng , Yuan Sibo , Liu Bin , Zhuang Guohong , Liu Zhongchen
Published: June 2012

Background

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is associated with anti-tumor immunity suppression. It is highly expressed in many tumors, and its expression can be regulated by the MAPK/MEK/ERK signaling pathway. The MAPK/MEK/ERK pathway has been reported to be a regulator in tumor occurrence, development and clonal expansion. External-signal regulated kinase (ERK) is a vital member of this pathway.

Results

The expression of DcR3 and ERK1/2 in tumor tissues of gastric cancer patients was significantly higher than the non-cancerous group (P < 0.05). There was no statistical difference among tumor tissues from patients with different ages or gender, and even of different differentiation (P > 0.05). However, in patients with stage I gastric cancer, the DcR3 and ERK1/2 levels were significantly lower than patients with more advanced stages.

Conclusions

DcR3 and ERK1/2 play a vital role in the development of gastric cancer, and they may be new markers for indicating the efficiency of gastric cancer treatment in the future.
Development and validation of a real-time PCR assay for detection and quantification of Tuber magnatum in soil
Authors: Iotti Mirco , Leonardi Marco , Oddis Marilena , Salerni Elena , Baraldi Elena , Zambonelli Alessandra
Published: June 2012

Background

Tuber magnatum, the Italian white truffle, is the most sought-after edible ectomycorrhizal mushroom. Previous studies report the difficulties of detecting its mycorrhizas and the widespread presence of its mycelium in natural production areas, suggesting that the soil mycelium could be a good indicator to evaluate its presence in the soil. In this study a specific real-time PCR assay using TaqMan chemistry was developed to detect and quantify T. magnatum in soil. This technique was then applied to four natural T. magnatum truffières located in different regions of Italy to validate the method under different environmental conditions.

Results

The primer/probe sets for the detection and quantification of T. magnatum were selected from the ITS rDNA regions. Their specificity was tested in silico and using qualitative PCR on DNA extracted from 25 different fungal species. The T. magnatum DNA concentration was different in the four experimental truffières and higher in the productive plots. T. magnatum mycelium was however also detected in most of the non-productive plots. Ascoma production during the three years of the study was correlated with the concentration of T. magnatum DNA.

Conclusions

Taken together, these results suggest that the specific real-time PCR assay perfected in this study could be an useful tool to evaluate the presence and dynamics of this precious truffle in natural and cultivated truffières.
Detection of mixed populations of wild-type and YMDD hepatitis B variants by pyrosequencing in acutely and chronically infected patients
Authors: Mello Francisco C A , Lago Bárbara V , Lewis-Ximenez Lia L , Fernandes Carlos A , Gomes Selma A
Published: June 2012

Background

Lamivudine (LAM) is associated with the highest known rate of resistance mutations among nucleotide analogs used to treat chronic hepatitis B virus (HBV) infection. Despite this, LAM continues in widespread use, especially in combination therapies. The primary LAM resistance mutation (rtM204V/I) occurs in the YMDD motif of HBV polymerase. The aim of this study was to characterize Brazilian HBV isolates from acute and chronic cases by direct sequencing, and to identify HBV quasispecies in the YMDD motif using a pyrosequencing method capable of detecting single-nucleotide polymorphisms. HBV DNA from serum samples of 20 individuals with acute HBV infection and 44 with chronic infection undergoing antiviral therapies containing LAM were analyzed by direct sequencing and pyrosequencing methods.

Results

Phylogenic analyses of direct-sequenced isolates showed the expected genotypes (A, D and F) for the Brazilian population in both acute and chronic infections. However, within genotype A isolates, subgenotype A2 was more frequently detected in acute cases than in chronic cases (P = 0.012). As expected, none of the individuals with acute hepatitis B had LAM-resistant isolates as a dominant virus population, whether detected by direct sequencing or pyrosequencing. However, pyrosequencing analyses showed that 45% of isolates (9/20) had minor subpopulations (4-17%) of LAM-resistant isolates. Among chronic patients undergoing LAM treatment, YMDD mutants were frequently found as a dominant virus population. In cases where wild-type virus was the dominant population, subpopulations of YMDD variants were usually found, demonstrating the complexity of HBV quasispecies.

Conclusions

YMDD variants were frequently detected as a minor population in acute HBV infection. The occurrence of pre-existing variants may lead to a high frequency of resistant mutants during antiviral therapy in the chronic phase. In chronic infection, detection of YMDD variants before virological or biochemical breakthrough might contribute to making better therapy choices and thus improving treatment outcome.
Retinal ganglion cell survival and axon regeneration in Wld
S
transgenic rats after optic nerve crush and lens injury
Authors: Lorber Barbara , Tassoni Alessia , Bull Natalie D , Moschos Marilita M , Martin Keith R
Published: June 2012

Background

We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals.

Results

As previously reported we found that the Wld

S
mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld

S
transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld

S
and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in Wld

S
transgenic rats.

Conclusions

RGC axon regeneration is similar between Wld

S
transgenic and wildtype rats, but Wld

S
transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the Wld

S
protein.
Decreased expression of extracellular matrix proteins and trophic factors in the amygdala complex of depressed mice after chronic immobilization stress
Authors: Jung Soonwoong , Lee Younghyurk , Kim Gyeongwha , Son Hyeonwi , Lee Dong Hoon , Roh Gu Seob , Kang Sang Soo , Cho Gyeong Jae , Choi Wan Sung , Kim Hyun Joon
Published: June 2012

Background

The amygdala plays an essential role in controlling emotional behaviors and has numerous connections to other brain regions. The functional role of the amygdala has been highlighted by various studies of stress-induced behavioral changes. Here we investigated gene expression changes in the amygdala in the chronic immobilization stress (CIS)-induced depression model.

Results

Eight genes were decreased in the amygdala of CIS mice, including genes for neurotrophic factors and extracellular matrix proteins. Among these, osteoglycin, fibromodulin, insulin-like growth factor 2 (Igf2), and insulin-like growth factor binding protein 2 (Igfbp2) were further analyzed for histological expression changes. The expression of osteoglycin and fibromodulin simultaneously decreased in the medial, basolateral, and central amygdala regions. However, Igf2 and Igfbp2 decreased specifically in the central nucleus of the amygdala. Interestingly, this decrease was found only in the amygdala of mice showing higher immobility, but not in mice displaying lower immobility, although the CIS regimen was the same for both groups.

Conclusions

These results suggest that the responsiveness of the amygdala may play a role in the sensitivity of CIS-induced behavioral changes in mice.
The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail
Authors: Yassi Rita , O’Grady Gregory , Paskaranandavadivel Nira , Du Peng , Angeli Timothy R , Pullan Andrew J , Cheng Leo K , Erickson Jonathan C
Published: June 2012

Background

Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail.

Results

GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite).

Conclusions

This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping.
Expression of proto-oncogene KIT is up-regulated in subset of human meningiomas
Authors: Saini Masum , Jha Ajaya Nand , Abrari Andleeb , Ali Sher
Published: June 2012

Background

KIT is a proto-oncogene involved in diverse neoplastic processes. Aberrant kinase activity of the KIT receptor has been targeted by tyrosine kinase inhibitor (TKI) therapy in different neoplasias. In all the earlier studies, KIT expression was reported to be absent in meningiomas. However, we observed KIT mRNA expression in some meningioma cases. This prompted us to undertake its detailed analyses in meningioma tissues resected during 2008–2009.

Methods

Tumor tissues and matched peripheral blood samples collected from meningioma patients were used for detailed molecular analyses. KIT expression was ascertained immunohistochemically and validated by immunoblotting. KIT and KITLG transcript levels were discerned by reverse transcription quantitative real-time PCR (RT-qPCR). Similarly, KIT amplification and allele loss were assessed by quantitative real-time (qPCR) and validated by fluorescence in situ hybridization (FISH) on the neoplastic tissues. Possible alterations of the gene at the nucleotide level were analyzed by sequencing.

Results

Contrary to earlier reports, KIT expression, was detected immunohistochemically in 20.6% meningioma cases (n = 34). Receptor (KIT) and ligand (KITLG) transcripts monitored by RT-qPCR were found to co-express (p = 0.048) in most of the KIT immunopositive tumors. 1/7 KIT positive meningiomas showed allele loss corroborated by reduced FISH signal in the corresponding neoplastic tissue. Sequence analysis of KIT showed M541L substitution in exon 10, in one of the immunopositive cases. However, its biological consequence remains to be uncovered.

Conclusions

This study clearly demonstrates KIT over-expression in the human meningiomas. The data suggest that up-regulated KIT transcription (p < 0.001), instead of gene amplification (p > 0.05), is a likely mechanism responsible for altered KIT expression. Thus, KIT is a potential candidate for detailed investigation in the context of meningioma pathogenesis.
Vitamin D3receptor is highly expressed in Hodgkin’s lymphoma
Authors: Renné Christoph , Benz Alexander H , Hansmann Martin L
Published: June 2012

Background

Hodgkin lymphoma (HL) is one of the most frequent lymphoma in the western world. Despite a good overall prognosis, some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as a possible diagnostic marker and potential therapeutic target in HL as well as in B-cell derived non-Hodgkin lymphoma (B-NHL).

Methods

We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of HL and 138 cases on several B-NHL entities.

Results

Vitamin D receptor is strongly expressed in tumor cells of HL, regardless of the sub entity with an overall positivity of 80% of all HL cases. In contrast, only about 17% of the analyzed origin-NHL showed positivity for vitamin D receptor. The detection of nuclear localization of vitamin D receptor in the tumor cells of HL suggests activated status of the vitamin D receptor.

Conclusions

Our study suggests VDR as a specific marker for tumor cells of HL, but not of B-NHL subtypes. Further, the observed nuclear localization suggests an activated receptor status in tumor cells of HL. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in HL.
Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1in laryngeal squamous cell carcinoma
Authors: Yang Min , Li Wei , Liu Yi-Ying , Fu Shuang , Qiu Guang-Bin , Sun Kai-Lai , Fu Wei-Neng
Published: June 2012

Background

MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated.

Methods

Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP).

Results

The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (−695 to −692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (−852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (−852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (−852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (−695 to −692) site prevented c-Myc from binding of the site and demethylation treatment of the 5′ flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01).

Conclusion

In summary, this study concluded that hypermethylation contributed to the transcriptional down-regulation of MYCT1 and could inhibit cancer cell differentiation in LSCC. DNA methylation of the CGCG site (−695 to −692) of MYCT1 altered the promoter activity by interfering with its binding to c-Myc in LSCC. Epigenetic therapy of reactivating MYCT1 by 5-aza should be further evaluated in clinical trails of LSCC.