bluuebunny/crossref_metadata_2025 huggingface dataset:
Militaristic Attitudes and the Use of Digital Games
Authors: Festl Ruth , Scharkow Michael , Quandt Thorsten
Published: August 2013

From their beginnings until today, digital games have been a substantial part of what has been labeled the “military–entertainment complex” deeply imbued with militaristic messages and imagery. Within cultivation research, this enhanced exposure to war and militarism is supposed to be associated with the adoption of military norms and thinking. Concepts on narrative persuasion specify this relationship between certain narratives and the adoption of story-inherent beliefs. Based on these theoretical concepts, the present study tries to investigate the relationship between aspects of gaming and militaristic attitudes. We carried out a representative survey of 4,500 gamers with an added control group of 500 nongamers. Militaristic attitudes were measured using a newly developed multidimensional militarism scale. Structural equation modeling did not reveal any relationship between gaming and militaristic attitudes. Moreover, neither the gaming type (multiplayer vs. single) nor the gaming frequency or a preference for shooter games was significantly related to militarism.
Gramsci and Games
Authors: Cassar Robert
Published: August 2013

The objective of this article is to highlight the relevance ideological debate plays in the study of popular culture texts and in particular in that of video games. Every text is a reflection of the ideological forces (cultural, economic, social, individual, etc.) generating it. Thus, ideology is essentially an omnipresent entity, which knows no boundaries of class, race, or cultural background. As a matter of fact, games are capable of reflecting ideological stances in a variety of ways. Throughout the first part of this article, we will revisit ideology from a Marxist perspective, that is, as a form of deception, manipulation, and enslavement and subsequently by moving away from such a deterministic/fatalistic approach and discussing it in the light of Gramsci’s theory of hegemony. By providing practical examples, this article will attempt to show how both ideological and hegemonic processes operate in the video game medium.
Palmar dislocation of the thumb metacarpophalangeal joint: report of four cases and a review of the literature
Authors: Senda H , Okamoto H
Published: August 2013

We report four cases of palmar dislocation of the thumb metacarpophalangeal joint and review of an additional 22 cases in the literature. Our four cases were associated with ligamentous injuries that prevented stable closed reduction. The patients were treated with open reduction and ligament repair and ultimately had a decreased range of motion. Our four cases and the 22 cases from literature fall into three types: Type A – stable joint (the metacarpophalangeal joint is stable, without severe ligament injury); Type B – tendon block (palmar displaced extensor tendons within the metacarpophalangeal joint prevents reduction); and Type C – joint instability (the metacarpophalangeal joint is unstable because of severe collateral ligament disruption). Type B is the most commonly reported type of palmar dislocation of the thumb metacarpophalangeal joint, with distinct features of the involvement of the collateral ligaments and failure of attempted manual reduction. The patients without severe collateral ligament disruption were managed with conservative treatment. The patients with interposition of extensor tendons and the patients with instability resulting from severe ligamentous injuries require surgical treatment.
Recent advances in asthma biomarker research
Authors: Leung Ting F. , Ko Fanny W. S. , Wong Gary W. K.
Published: August 2013

Asthma is characterized by recurrent and reversible airflow obstruction, which is routinely monitored by history and physical examination, spirometry and home peak flow diaries. As airway inflammation is central to asthma pathogenesis, its monitoring should be part of patient management plans. Fractional exhaled nitric oxide level (FeNO) is the most extensively studied biomarker of airway inflammation, and FeNO references were higher in Chinese (Asians) than Whites. Published evidence was inconclusive as to whether FeNO is a useful management strategy for asthma. Other biomarkers include direct (histamine, methacholine) and indirect (adenosine, hypertonic saline) challenges of bronchial hyperresponsiveness (BHR), induced sputum and exhaled breath condensate (EBC). A management strategy that normalized sputum eosinophils among adult patients resulted in reductions of BHR and asthma exacerbations. However, subsequent adult and pediatric studies failed to replicate these benefits. Asthma phenotypes as defined by inflammatory cell populations in sputum were also not stable over a 12-month period. A recent meta-analysis concluded that induced sputum is not accurate enough to be applied in routine monitoring of childhood asthma. There is poor correlation between biomarkers that reflect different asthma dimensions: spirometry (airway caliber), BHR (airway reactivity) and FeNO or induced sputum (airway inflammation). Lastly, EBC is easily obtained noninvasively by cooling expired air. Many biomarkers ranging from acidity (pH), leukotrienes, aldehydes, cytokines to growth factors have been described. However, significant overlap between groups and technical difficulty in measuring low levels of inflammatory molecules are the major obstacles for EBC research. Metabolomics is an emerging analytical method for EBC biomarkers. In conclusion, both FeNO and induced sputum are useful asthma biomarkers. However, they will only form part of the clinical picture. Longitudinal studies with focused hypotheses and well-designed protocols are needed to establish the roles of these biomarkers in asthma management. The measurement of biomarkers in EBC remains a research tool.
Screening colonoscopy bowel preparation: experience in an urban minority population
Authors: Basch Corey H. , Basch Charles E. , Wolf Randi L. , Zybert Patricia , Lebwohl Benjamin , Shmukler Celia , Neugut Alfred I. , Shea Steven
Published: August 2013

Methods:

Suboptimal bowel preparation, present in over 20% of colonoscopies, can severely compromise the effectiveness of the colonoscopy procedure. We surveyed 93 primarily urban minority men and women who underwent asymptomatic ‘screening’ colonoscopy regarding their precolonoscopy bowel-preparation experience.

Results:

Print materials alone (39.8%) and in-person verbal instructions alone (35.5%) were reportedly the most common modes of instruction from the gastroenterologists. Liquid-containing laxative (70.6%) was the most common laxative agent; a clear liquid diet (69.6%) the most common dietary restriction. Almost half of the participants mentioned ‘getting the laxative down’ as one of the hardest parts of the preparation; 40.9% mentioned dietary restrictions. The 24.7% who mentioned ‘understanding the instructions’ as one of the hardest parts were more likely to be non-US born and to have lower education and income. There was no relationship between difficulty in understanding instructions and mode of instruction or preparation protocol. One quarter suggested that a smaller volume and/or more palatable liquid would have made the preparation easier. Three quarters agreed that it would have been helpful to have someone to guide them through the preparation process.

Conclusions:

These findings suggest a variety of opportunities for both physician- and patient-directed educational interventions to promote higher rates of optimal colonoscopy bowel preparation.
Outdoor respirable particulate matter and the lung function status of residents of selected communities in Ibadan, Nigeria
Authors: Ana GREE , Odeshi TA , Sridhar MKC , Ige MO
Published: August 2013

Background:

Ambient air pollution remains a major public health hazard in urban communities. In Nigeria, air quality management especially in the urban centres, is fraught with enormous challenges including limited data. We assessed the outdoor respirable particulate matter (PM10) concentration and the pulmonary function status of residents in four selected communities in Ibadan.

Methods:

A cross-sectional study design was employed. Four locations – Ojoo Park (OP = high traffic area), Bodija Market (BM = commercial area), Oluyole Estate (OE = industrial area) and the University of Ibadan (UI = academic community – reference) – were selected based on varying intensities of urban activity. PM10 levels were recorded in the morning and afternoon for 12 weeks between January and March 2008. Lung function status (FEV1) of 140 randomly selected participants was measured. Daily mean of PM10 levels were compared with WHO guideline limits. Data analysis was done using descriptive, χ2, ANOVA and Spearman-rank correlation tests at 5% level of significance.

Results:

For all sites, PM10 concentration was generally higher in the afternoon. The highest daily mean PM10 concentration was recorded at BM, followed by OP, OE and UI. These values when compared with WHO guideline limits showed: BM eightfold > OP sevenfold > OE sixfold > UI fivefold ( p < .05). Weekly mean PM10 levels and mean FEV1(obs) gave the following order: UI > OE > OP > BM. There was a significant negative correlation between PM10 burden and FEV1(obs) across the study locations ( r =-0.371, p < .05).

Conclusion:

Most of the locations with higher particulate burden were observed to have declining lung function status. A longitudinal study to establish more robust associations is advocated.
New combinations and immunotherapies for melanoma: latest evidence and clinical utility
Authors: Menzies Alexander M. , Long Georgina V.
Published: August 2013

Until recently there was no effective systemic therapy for metastatic melanoma. Increased understanding of tumor biology and immune regulation has led to the development of drugs targeting the mitogen-activated protein kinase (MAPK) pathway (BRAF inhibitors and MEK inhibitors) and T-cell regulation (CTLA4 antibodies). These drugs are the new standard of care, however barriers to better patient outcomes include limited responses and significant toxicities (CTLA4 antibodies) and lack of durability in the majority of cases (BRAF and MEK inhibitors). This review discusses the next stages of development of treatments in melanoma, including immune checkpoint blocking drugs targeting the PD-1/PD-L1 axis, and the use of BRAF and MEK inhibitors in combination. Both approaches lead to a higher proportion of durable responses coupled with less toxicity. In an effort to improve outcomes even further, clinical trials of combinations of MAPK inhibitors, immunotherapies and other signal pathway inhibitors are underway. Adjuvant studies of many of these drugs have commenced, with the hope of also improving outcomes in patients with early-stage melanoma.
Factors Influencing Ball-Player Impact Probability in Youth Baseball
Authors: Matta Philip A. , Myers Joseph B. , Sawicki Gregory S.
Published: August 2013

Background:

Altering the weight of baseballs for youth play has been studied out of concern for player safety. Research has shown that decreasing the weight of baseballs may limit the severity of both chronic arm and collision injuries. Unfortunately, reducing the weight of the ball also increases its exit velocity, leaving pitchers and nonpitchers with less time to defend themselves. The purpose of this study was to examine impact probability for pitchers and nonpitchers.

Hypothesis:

Reducing the available time to respond by 10% (expected from reducing ball weight from 142 g to 113 g) would increase impact probability for pitchers and nonpitchers, and players’ mean simple response time would be a primary predictor of impact probability for all participants.

Study Design:

Nineteen subjects between the ages of 9 and 13 years performed 3 experiments in a controlled laboratory setting: a simple response time test, an avoidance response time test, and a pitching response time test.

Methods:

Each subject performed these tests in order. The simple reaction time test tested the subjects’ mean simple response time, the avoidance reaction time test tested the subjects’ ability to avoid a simulated batted ball as a fielder, and the pitching reaction time test tested the subjects’ ability to avoid a simulated batted ball as a pitcher.

Results:

Reducing the weight of a standard baseball from 142 g to 113 g led to a less than 5% increase in impact probability for nonpitchers. However, the results indicate that the impact probability for pitchers could increase by more than 25%.

Conclusion:

Pitching may greatly increase the amount of time needed to react and defend oneself from a batted ball.

Clinical Relevance:

Impact injuries to youth baseball players may increase if a 113-g ball is used.
Comparison of IKDC and SANE Outcome Measures Following Knee Injury in Active Female Patients
Authors: Winterstein Andrew P. , McGuine Timothy A. , Carr Kathleen E. , Hetzel Scott J.
Published: August 2013

Background:

Knee injury among young, active female patients remains a public health issue. Clinicians are called upon to pay greater attention to patient-oriented outcomes to evaluate the impact of these injuries. Little agreement exists on which outcome measures are best, and clinicians cite several barriers to their use. Single Assessment Numerical Evaluation (SANE) may provide meaningful outcome information while lessening the time burden associated with other patient-oriented measures.

Hypothesis:

The SANE and International Knee Documentation Committee (IKDC) scores would be strongly correlated in a cohort of young active female patients with knee injuries from preinjury through 1-year follow-up and that a minimal clinically important difference (MCID) could be calculated for the SANE score.

Study Design:

Observational prospective cohort.

Methods:

Two hundred sixty-three subjects completed SANE and IKDC at preinjury by recall, time of injury, and 3, 6, and 12 months postinjury. Pearson correlation coefficients were used to assess the association between SANE and IKDC. Repeated-measures analysis of variance was used to determine differences in SANE and IKDC over time. MCID was calculated for SANE using IKDC MCID as an anchor.

Results:

Moderate to strong correlations were seen between SANE and IKDC (0.65-0.83). SANE, on average, was 2.7 (95% confidence interval, 1.5-3.9; P < 0.00) units greater than IKDC over all time points. MCID for the SANE was calculated as 7 for a 6-month follow-up and 19 for a 12-month follow-up.

Conclusion:

SANE scores were moderately to strongly correlated to IKDC scores across all time points. Reported MCID values for the SANE should be utilized to measure meaningful changes over time for young, active female patients with knee injuries.

Clinical Relevance:

Providing clinicians with patient-oriented outcome measures that can be obtained with little clinician and patient burden may allow for greater acceptance and use of outcome measures in clinical settings.
Aggressive Acts Increase Commitment to New Groups
Authors: Toosi Negin R. , Masicampo E. J. , Ambady Nalini
Published: August 2013

How do individuals who switch between opposing sides develop a sense of commitment to their new groups? Study 1 examined these dynamics in a live-action tag game known as Humans versus Zombies, in which players transitioned from being Human to being Zombie, thus turning against their former fellow Humans. Study 2 examined data from professional basketball players in the National Basketball Association who moved to a new team and had to play against their former team. Aggressive acts against former group members in these competitive settings determined commitment to the new group above and beyond other factors. Aggressive acts against former teammates, such as simulated killing (Study 1) and blocked shots (Study 2), promoted more positive self-reported attitudes toward the new group (Study 1) and more collaboration with new group members in the form of assists (Study 2).
Teriflunomide in relapsing multiple sclerosis: therapeutic utility
Authors: Freedman Mark S.
Published: August 2013

Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS.
Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome
Authors: Sood Ruchit , Ford Alexander C.
Published: August 2013

Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS) are functional disorders of the lower gastrointestinal tract. Their prevalence in the general population is between 5% and 20%. Both disorders are chronic, with a relapsing and remitting natural history. The medical treatment of both conditions is unsatisfactory at present, and they represent a huge burden to the health service. Linaclotide is a first-in-class minimally adsorbed, 14-amino-acid peptide agonist of guanylate cyclase C. The drug acts on the intestinal enterocyte. As a consequence of this, intestinal fluid secretion is increased and intestinal transit is accelerated. The efficacy of linaclotide has been studied in both CIC and constipation-predominant IBS (IBS-C). Randomized controlled trials consistently demonstrate that the drug is effective in the treatment of CIC and IBS-C, across a wide range of continuous and dichotomous endpoints. The number needed to treat with linaclotide to prevent one patient with CIC or IBS-C failing to respond to therapy is between 5 and 8 in studies that have reported these data. Overall, in the majority of trials, total numbers of adverse events have been no more frequent with linaclotide, but rates of diarrhoea have been consistently higher. While the drug is clearly effective in the treatment of CIC, there are other evidence-based therapies available, and head-to-head efficacy and cost-effectiveness studies are therefore required to further delineate the role of linaclotide in the treatment of the condition. In IBS-C there are no other licensed therapies available, and linaclotide therefore represents a novel treatment with great promise.
Calcium supplements and cardiovascular risk: 5 years on
Authors: Bolland Mark J. , Grey Andrew , Reid Ian R.
Published: August 2013

Calcium supplements have been widely used by older men and women. However, in little more than a decade, authoritative recommendations have changed from encouraging the widespread use of calcium supplements to stating that they should not be used for primary prevention of fractures. This substantial shift in recommendations has occurred as a result of accumulated evidence of marginal antifracture efficacy, and important adverse effects from large randomized controlled trials of calcium or coadministered calcium and vitamin D supplements. In this review, we discuss this evidence, with a particular focus on increased cardiovascular risk with calcium supplements, which we first described 5 years ago. Calcium supplements with or without vitamin D marginally reduce total fractures but do not prevent hip fractures in community-dwelling individuals. They also cause kidney stones, acute gastrointestinal events, and increase the risk of myocardial infarction and stroke. Any benefit of calcium supplements on preventing fracture is outweighed by increased cardiovascular events. While there is little evidence to suggest that dietary calcium intake is associated with cardiovascular risk, there is also little evidence that it is associated with fracture risk. Therefore, for the majority of people, dietary calcium intake does not require close scrutiny. Because of the unfavorable risk/benefit profile, widespread prescribing of calcium supplements to prevent fractures should be abandoned. Patients at high risk of fracture should be encouraged to take agents with proven efficacy in preventing vertebral and nonvertebral fractures.
Grand regional narratives
Authors: Rigg Jonathan
Published: August 2013

This commentary addresses four themes relevant to Alexander Murphy’s (2013) paper. First, with reference to the East Asian region, the commentary cautions against reductionist grand regional narratives, while lauding, clarifying and illuminating narratives. These, and second, can either be built from the ground up based on quite localised studies from which clarifying conceptual framings can be drawn or by generalising down. The former are seen as often more instructive than the latter. Third, the commentary makes a case for middle order generalisation that occupies an explanatory space between grand theorising/cross-country generalisation on the one hand and microassertions on the other. Finally, the commentary takes issue with Murphy’s critique of the term ‘Global South’, which, it is argued, he problematically misrepresents.
Where in the (capitalist) world (economy) are regional narratives?
Authors: Flint Colin
Published: August 2013

General support is given for the call by Alexander Murphy for a study of regions to enable geographers to engage in public debates. However, Murphy’s emphasis upon narrative is challenged and an argument is made for a theoretical framework within which to situate analysis of regions. Moreover, the “meso” scale of the region demands consideration of a larger, or “macro,” scale. World-systems theory is advanced as a framework that defines the global scale as the capitalist world-economy in a way that situates regions and gives meaning to their form and interaction. The empirical approach offered by world-systems theory enhances Murphy’s call for regional narratives and enables geographers to engage in public debates.
The struggle over geography
Authors: Castree Noel
Published: August 2013

This commentary is sympathetic to Murphy’s (2013) call for more ‘grand regional narrative’ in a public key. However, by failing to recognise the root causes of, and prevailing obstacles to, change, his call risks being purely declarative. I argue that only a few, typically established, geographers will be willing and able to occupy the ideational territory currently populated by the likes of Robert Kaplan. Even so, a few is better than none, and I also argue that teaching offers a more feasible, if indirect, arena in which public thinking about world geography can be shaped in ways consistent with Murphy’s vision.
Advancing geographical understanding
Authors: Murphy Alexander B
Published: August 2013

Work in contemporary human geography only occasionally addresses the grand, empirically based regional narratives that figure prominently in the public debate. Since such narratives have a powerful influence on ideas and actions, whether and how geographers speak to them are important questions for the effort to promote “public geographies.” Three case studies illustrate what is lost if grand regional narratives are not addressed more directly by human geographers: one focused on how regions are characterized (Southwest Asia/North Africa), one on how regions are compared (the contemporary European Union and the early United States), and one on how regionalization schemes are deployed (the “North–South” dichotomization of the world). An expanded geographic engagement with grand regional narratives requires periodic pulling back from scrutiny of individual cases to consider broader patterns and process, and a heightened effort not just to critique, but to propose concrete alternatives.
Challenges and opportunities of a revived regional engagement
Authors: Murphy Alexander B
Published: August 2013

In response to the commentaries on the paper on geographic engagement with grand regional narratives (Murphy, 2013), the author makes four basic points. The audiences for grand regional narratives should not be seen solely as policy elites; by extension, a variety of types of geographic scholarship can contribute to shaping large-scale regional narratives. Second, grand regional narratives necessarily have theoretical underpinnings, and there is no necessary opposition between them and microlevel studies. Third, geographically informed grand regional narratives can be produced that do not fall into essentialist traps, and they have much to contribute to public debate. Finally, there are significant constraints on efforts to shape grand regional narratives, but some effort to challenge those constraints is possible and important.
Here, there, everywhere
Authors: Howitt Richard
Published: August 2013

The dominant discourses of Anglo-American economic geography universalised certain particulars in ways that rendered as archetypal some things that were perhaps better treated as marginal, or at least locally specific. Simultaneously, those dominant discourses rendered as marginal, unimportant or absent, things that are central to economic geographies in a range of places. This commentary reflects on key elements of the foundations for a distinctive Antipodean contribution to wider debates in human geography and the value of such debate to other marginalised discourses in the discipline.
Always engaging with others
Authors: Dombroski Kelly
Published: August 2013

Although sometimes thought of as peripheral to the ‘centres’ of economic geography in the Anglo-American ‘North’, Australian and New Zealand geographers have already made important contributions to global economic geography. In this commentary on Wray et al.’s (2013) paper, I interpret their Antipodean economic geography project as a performative intervention that works to queer economic geography. I extend their project through asking what an Antipodean economic geography might become, and how we might extend its usefulness in this era of anthropogenic climate change.
Defending Antipodean economic geography
Authors: Wray Felicity , Dufty-Jones Rae
Published: August 2013

In response to the commentaries, we reflect on the pitfalls and opportunities that come with identifying and naming ‘Antipodean economic geographies’ and in particular emphasise the practical aspects of this decision. We also critically reflect on suggestions that we have brought such knowledges into a set of market relations, citing how the recently published International Benchmarking Review of UK Human Geography gives added salience to the intentions of our original paper. Finally, we note the useful ground clearing that these commentaries make for future debates around the politics and whereness of economic geographical knowledge production in new global contexts.
Neither here nor there or always here and there? Antipodean reflections on economic geography
Authors: Wray Felicity , Dufty-Jones Rae , Gibson Chris , Larner Wendy , Beer Andrew , Heron Richard Le , O’Neill Phillip
Published: August 2013

This paper emerged from discussions held over a two-day symposium hosted by the University of Western Sydney and the Institute of Australian Geographers in December 2011. Drawing on contemporary themes in economic geography around postcolonial theory and a concern with the histories of the sub-discipline, the symposium sought to triangulate these discourses using Raewyn Connell’s (2006, 2007a, 2007b) concept of ‘Southern Theory’ as a means of beginning a process of critical reflection about the types of economic geographies that are produced from and in the ‘Antipodes’. After introducing these debates and presenting a critical reflection on how Connell’s Southern Theory potentially provides a useful means of bringing them into conversation, the paper presents five considerations from geographers who have made significant contributions to contemporary economic geography understandings, drawing on, in various ways, their Antipodean positionality. The paper assesses to what extent are Antipodean economic geography knowledges: (i) unique and embedded in specific conditions and events, (ii) inexorably tied to other economic geographical knowledges produced elsewhere and (iii) how Antipodean economic geography knowledges have been exported and assembled within and beyond the discipline of geography.
“I Am Blacker Than You”
Authors: Okonofua Benjamin Aigbe
Published: August 2013

This paper attempts to place the African immigrant and the African American in the context of their conditions in the United States. It addresses the issue of Americanization and the development of multiple identities that is fundamental to the contestation of “Blackness” in the United States. More importantly, the study discusses resource allocation and appropriation as critical to understanding the schisms between the African immigrant and the African American, focusing especially on how the conflict and tension potentially benefits other racial categories. It highlights the fact that conflict and tension between both groups result directly from the dominant White racial framing, wherein powerless groups unable to effectively challenge the forces that oppress them, attack themselves or people like themselves. To explain this complex interaction between Whites, African immigrants, and African Americans, this paper develops the theory of manipulative deflection, the central tenet of which is the subjective experience of deprivation that diminishes the construction of a holistic Black identity and produces confusion and conflict among Blacks in the United States.
Ikaros is required to survive positive selection and to maintain clonal diversity during T-cell development in the thymus
Authors: Tinsley Kevin W. , Hong Changwan , Luckey Megan A. , Park Joo-Young , Kim Grace Y. , Yoon Hee-won , Keller Hilary R. , Sacks Andrew J. , Feigenbaum Lionel , Park Jung-Hyun
Published: August 2013

Key Points

Ikaros suppresses thymocyte proliferation but induces antiapoptotic molecule expression upon TCR-induced positive selection. Ikaros function is required to prevent clonal expansion and to maintain a random TCR repertoire during thymocyte differentiation.
MP4CO, a pegylated hemoglobin saturated with carbon monoxide, is a modulator of HO-1, inflammation, and vaso-occlusion in transgenic sickle mice
Authors: Belcher John D. , Young Mark , Chen Chunsheng , Nguyen Julia , Burhop Kenneth , Tran Phuc , Vercellotti Gregory M.
Published: August 2013

Key Points

Carbon monoxide treatment of murine sickle mice can ameliorate inflammation and vaso-occlusion. MP4CO induces heme oxygenase-1 and Nrf2 to mediate these salutatory effects.
Human regulatory T cells against minor histocompatibility antigens: ex vivo expansion for prevention of graft-versus-host disease
Authors: Veerapathran Anandharaman , Pidala Joseph , Beato Francisca , Betts Brian , Kim Jongphil , Turner Joel G. , Hellerstein Marc K. , Yu Xue-Zhong , Janssen William , Anasetti Claudio
Published: August 2013

Key Points

This is the first report about the detection of human Tregs specific for minor histocompatibility antigens. We detected, quantified, and cloned mHA-specific Tregs and expanded these potent Tregs in sufficient numbers for use in human transplantation.
How T cells trigger the dissociation of the endothelial receptor phosphatase VE-PTP from VE-cadherin
Authors: Vockel Matthias , Vestweber Dietmar
Published: August 2013

Key Points

The endothelial leukocyte receptor VCAM-1 triggers opening of endothelial junctions via dissociation of VE-PTP from VE-cadherin. VCAM-1 and VEGF signaling use a similar signaling pathway to trigger the dissociation of VE-PTP from VE-cadherin.
Influence of proband’s characteristics on the risk for venous thromboembolism in relatives with factor V Leiden or prothrombin G20210A polymorphisms
Authors: Bucciarelli Paolo , De Stefano Valerio , Passamonti Serena M. , Tormene Daniela , Legnani Cristina , Rossi Elena , Castaman Giancarlo , Simioni Paolo , Cini Michela , Martinelli Ida
Published: August 2013

Key Points

The risk for venous thromboembolism in relatives with factor V Leiden or prothrombin G20210A differs according to the probands’ selection. Relatives belonging to families with heterozygous probands with venous thromboembolism have the highest risk for venous thromboembolism.
Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein
Authors: Wang Chung-Jen , Chen Chien-Chih , Tsay Huey-Jen , Chiang Feng-Yi , Wu Mine-Fong , Shiao Young-Ji
Published: August 2013

Background

Microglial inflammation may significantly contribute to the pathology of Alzheimer’s disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid β protein (Aβ)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed.

Results

Lipopolysaccharide (LPS), Interferon-γ (IFN-γ), fibrillary Aβ (fAβ), or oligomeric Aβ (oAβ) were used to activate microglia. LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.

The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ. On the other hand, oAβ effectively activated the ramified microglia in mixed glial culture by observing the morphological alteration of the microglia from ramified to amoeboid. CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance. Results are expressed as mean ± S.D. and were analyzed by ANOVA with post-hoc multiple comparisons with a Bonferroni test.

Conclusions

The components of Cudrania cochinchinensis including CC-EW and CCB are potential for novel therapeutic intervention for Alzheimer’s disease.
Transcriptional abundance is not the single force driving the evolution of bacterial proteins
Authors: Wei Wen , Zhang Tao , Lin Dan , Yang Zu-Jun , Guo Feng-Biao
Published: August 2013

Background

Despite rapid progress in understanding the mechanisms that shape the evolution of proteins, the relative importance of various factors remain to be elucidated. In this study, we have assessed the effects of 16 different biological features on the evolutionary rates (ERs) of protein-coding sequences in bacterial genomes.

Results

Our analysis of 18 bacterial species revealed new correlations between ERs and constraining factors. Previous studies have suggested that transcriptional abundance overwhelmingly constrains the evolution of yeast protein sequences. This transcriptional abundance leads to selection against misfolding or misinteractions. In this study we found that there was no single factor in determining the evolution of bacterial proteins. Not only transcriptional abundance (codon adaptation index and expression level), but also protein-protein associations (PPAs), essentiality (ESS), subcellular localization of cytoplasmic membrane (SLM), transmembrane helices (TMH) and hydropathicity score (HS) independently and significantly affected the ERs of bacterial proteins. In some species, PPA and ESS demonstrate higher correlations with ER than transcriptional abundance.

Conclusions

Different forces drive the evolution of protein sequences in yeast and bacteria. In bacteria, the constraints are involved in avoiding a build-up of toxic molecules caused by misfolding/misinteraction (transcriptional abundance), while retaining important functions (ESS, PPA) and maintaining the cell membrane (SLM, TMH and HS). Each of these independently contributes to the variation in protein evolution.
AFLP-based genetic mapping of the “bud-flowering” trait in heather (Calluna vulgaris)
Authors: Behrend Anne , Borchert Thomas , Spiller Monika , Hohe Annette
Published: August 2013

Background

Calluna vulgaris is one of the most important landscaping plants produced in Germany. Its enormous economic success is due to the prolonged flower attractiveness of mutants in flower morphology, the so-called bud-bloomers. In this study, we present the first genetic linkage map of C. vulgaris in which we mapped a locus of the economically highly desired trait “flower type”.

Results

The map was constructed in JoinMap 4.1. using 535 AFLP markers from a single mapping population. A large fraction (40%) of markers showed distorted segregation. To test the effect of segregation distortion on linkage estimation, these markers were sorted regarding their segregation ratio and added in groups to the data set. The plausibility of group formation was evaluated by comparison of the “two-way pseudo-testcross” and the “integrated” mapping approach. Furthermore, regression mapping was compared to the multipoint-likelihood algorithm. The majority of maps constructed by different combinations of these methods consisted of eight linkage groups corresponding to the chromosome number of C. vulgaris.

Conclusions

All maps confirmed the independent inheritance of the most important horticultural traits “flower type”, “flower colour”, and “leaf colour”. An AFLP marker for the most important breeding target “flower type” was identified. The presented genetic map of C. vulgaris can now serve as a basis for further molecular marker selection and map-based cloning of the candidate gene encoding the unique flower architecture of C. vulgaris bud-bloomers.
A comprehensive metatranscriptome analysis pipeline and its validation using human small intestine microbiota datasets
Authors: Leimena Milkha M , Ramiro-Garcia Javier , Davids Mark , van den Bogert Bartholomeus , Smidt Hauke , Smid Eddy J , Boekhorst Jos , Zoetendal Erwin G , Schaap Peter J , Kleerebezem Michiel
Published: August 2013

Background

Next generation sequencing (NGS) technologies can be applied in complex microbial ecosystems for metatranscriptome analysis by employing direct cDNA sequencing, which is known as RNA sequencing (RNA-seq). RNA-seq generates large datasets of great complexity, the comprehensive interpretation of which requires a reliable bioinformatic pipeline. In this study, we focus on the development of such a metatranscriptome pipeline, which we validate using Illumina RNA-seq datasets derived from the small intestine microbiota of two individuals with an ileostomy.

Results

The metatranscriptome pipeline developed here enabled effective removal of rRNA derived sequences, followed by confident assignment of the predicted function and taxonomic origin of the mRNA reads. Phylogenetic analysis of the small intestine metatranscriptome datasets revealed a strong similarity with the community composition profiles obtained from 16S rDNA and rRNA pyrosequencing, indicating considerable congruency between community composition (rDNA), and the taxonomic distribution of overall (rRNA) and specific (mRNA) activity among its microbial members. Reproducibility of the metatranscriptome sequencing approach was established by independent duplicate experiments. In addition, comparison of metatranscriptome analysis employing single- or paired-end sequencing methods indicated that the latter approach does not provide improved functional or phylogenetic insights. Metatranscriptome functional-mapping allowed the analysis of global, and genus specific activity of the microbiota, and illustrated the potential of these approaches to unravel syntrophic interactions in microbial ecosystems.

Conclusions

A reliable pipeline for metatransciptome data analysis was developed and evaluated using RNA-seq datasets obtained for the human small intestine microbiota. The set-up of the pipeline is very generic and can be applied for (bacterial) metatranscriptome analysis in any chosen niche.
OmpR and RcsB abolish temporal and spatial changes in expression of flhD in Escherichia coli Biofilm
Authors: Samanta Priyankar , Clark Emily R , Knutson Katie , Horne Shelley M , Prüß Birgit M
Published: August 2013

Background

Biofilms are communities of bacteria that are characterized by specific phenotypes, including an increased resistance towards anti-microbials and the host immune system. This calls for the development of novel biofilm prevention and treatment options to combat infectious disease. In Escherichia coli, numerous global regulators have been implicated in the control of biofilm associated cell surface organelles. These include the flagellar regulator FlhD/FlhC, the osmoregulator EnvZ/OmpR, and the colanic acid activator RcsCDB. Using flow cell technology and fluorescence microscopy, we determined the temporal expression from flhD::gfp, ompR::gfp, and rcsB::gfp in E. coli biofilm, as well as the impact of the negative regulation of flhD by OmpR and RcsB. Spatial gene expression was investigated from flhD::gfp.

Results

The temporal gene expression profile for flhD yielded an early peak at 12 h, a minimum of expression at 35 h, and a second increase in expression towards 51 h of biofilm development. In contrast, the ompR profile showed a peak at 35 h. A mutation in ompR abolished time dependence of flhD expression after the initial growth period of 12 h. Intriguingly, rcsB expression did not correlate inversely with flhD expression, yet a mutation in rcsB abolished time dependence of flhD expression as well. Spatially, expression of flhD was highest in the outermost layer of the biofilm in the parent strain. In ompR and rcsB mutants, flhD was expressed throughout the biofilm. Mutations in both, ompR and rcsB increased flhD expression throughout all temporal and spatial experiments. This increase was paralleled by reductions in biofilm amounts at four tested time points.

Conclusion

Our data lead to the conclusion that FlhD/FlhC and its regulation by OmpR and RcsB may be our first target mechanism for the development of novel biofilm prevention and treatment techniques.
OECs transplantation results in neuropathic pain associated with BDNF regulating ERK activity in rats following cord hemisection
Authors: Lang Bing-Chen , Zhang Zhuo , Lv Long-Yun , Liu Jin , Wang Ting-Yong , Yang Ling-Hui , Liao Da-Qing , Zhang Wen-Sheng , Wang Ting-Hua
Published: August 2013

Background

The olfactory ensheathing cells (OECs) derived from olfactory bulb (OB) may improve motor function after transplantation in injured spinal cord. However, the effects of OEC transplantation on sensory function have not been reported yet. The purpose of this study is to investigate whether OEC transplantation could affect the sensory function and to analyze the underlying mechanism.

Results

OEC transplantation into the hemisected spinal cords can result in hyperalgesia, indicated by radiant and mechanical stimuli towards the plantar surface in rats. This could be associated with upregulation of Brain Derived Neurotrophic Factor (BDNF), indicated by RT-PCR. Immunofluorecent staining showed that BDNF was mainly located in the neurons of the laminas I and II of the dorsal horn. Moreover, a notable upregulation on the level of p-ERK (phosphorylation of extracellular signal-regulated kinase), the downstream molecule of BDNF, was detected by using Western Blot. These findings indicate that the increased BDNF level associated with the p-ERK was possibly involved in neuropathic pain in hemisected spinal cord subjected to OEC transplantation.

Conclusions

The transplantation of OECs may induce the noticeable pain hypersensitivity in rats after hemisected spinal cord injury, and the possible mechanism may be associated with the phosphorylation of ERK and the activated BDNF overexpression.
Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection
Authors: Wu Yong , Collier Lauren , Qin Weiping , Creasey Graham , Bauman William A , Jarvis Jonathan , Cardozo Christopher
Published: August 2013

Background

Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA).

Results

ES increased expression of Hey1 and Pitx2 suggesting increased Notch and Wnt signaling, respectively, but did not normalize RCAN1.4, a measure of calcineurin/NFAT signaling, or PGC-1ß mRNA levels. ES increased PGC-1α expression but not that of slow myofibrillar genes. Microarray analysis showed that after ES, genes coding for calcium binding proteins and nicotinic acetylcholine receptors were increased, and the expression of genes involved in blood vessel formation and morphogenesis was altered. Of the 165 genes altered by ES only 16 were also differentially expressed after GA, of which 12 were altered in the same direction by ES and GA. In contrast to ES, GA induced expression of genes related to oxidative phosphorylation.

Conclusions

Notch and Wnt signaling may be involved in ES-induced increases in the mass of paralyzed muscle. Molecular adaptations of paralyzed soleus to resistance exercise are delayed or defective compared to normally innervated muscle.